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{{DiseaseDisorder infobox |
__NOTOC__
  Name          = Leukocytosis |
{{SI}}                                                                 
  ICD10          = {{ICD10|D|72|8|d|70}} |
{{CMG}}; {{AE}} {{MV}} {{LG}}; {{GRR}} {{Nat}}
  ICD9          = {{ICD9|288.3}}, {{ICD9|288.6x}} |
  Image          = |
{{SK}}  Elevated white blood cell count; Right-shift leukocytosis; Left-shift leukocytosis
  Caption        = |
  ICDO          = |
==Overview==
  OMIM          = |
 
  DiseasesDB    = 33024 |
'''Leukocytosis''' is the elevation of the white blood cell count above the normal range (greater than 11,000 per mm3). Leukocytosis is frequently a sign of an [[Inflammation|inflammatory response]], most commonly the result of [[infection]], but may also occur following certain parasitic infections, [[bone tumor|bone tumors]], strenuous exercise, emotional stress, pregnancy,  anesthesia, and epinephrine administration. Leukocytosis may be classified into 5 sub-types: [[neutrophilia]] (most common), [[lymphocytosis]], [[monocytosis]], [[eosinophilia]], and [[basophilia]]. Other classifications include: Left shift or right shift leukocytosis. The pathogenesis of leukocytosis is characterized by the increase of leukocytes (primarily neutrophils), followed by the proliferation and release of granulocyte and monocyte precursors in the bone marrow, which is then stimulated by several products of inflammation including [[C3a]] and [[G-CSF]].<ref name="pmid24750674">{{cite journal |vauthors=Chabot-Richards DS, George TI |title=Leukocytosis |journal=Int J Lab Hematol |volume=36 |issue=3 |pages=279–88 |year=2014 |pmid=24750674 |doi=10.1111/ijlh.12212 |url=}}</ref>
  MedlinePlus    = |
 
  eMedicineSubj  = |
==Historical Perspective==
  eMedicineTopic = |
*Leukocytosis was first discovered by Paul Kautchakoff in 1846.<ref name="pmid24750674">{{cite journal |vauthors=Chabot-Richards DS, George TI |title=Leukocytosis |journal=Int J Lab Hematol |volume=36 |issue=3 |pages=279–88 |year=2014 |pmid=24750674 |doi=10.1111/ijlh.12212 |url=}}</ref>
}}
 
{{SI}}
==Classification==
{{CMG}}; {{AOEIC}} {{LG}}
*Leukocytosis may be classified into 5 sub-types:<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
:*[[Neutrophilia]] (most common)
:*[[Lymphocytosis]]
:*[[Monocytosis]]
:*[[Eosinophilia]]
:*[[Basophilia]].


'''''Synonyms and keywords:''''' Granulocytosis, neutrophilia
*Leukocytosis may also be classified into 2 groups:<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
:*'''Left shift''' (most common)
::*Immature leukocytes increase
::*Proliferation and release of [[granulocyte]] and [[monocyte]] precursors in the [[bone marrow]]
::*Usually stimulated by several products of inflammation including [[C3a]] and [[Granulocyte colony stimulating factor|G-CSF]]
:*'''Right shift'''
::*Reduced count or lack of "young [[neutrophils]]"
::*Associated with the presence of "giant [[Neutrophil|neutrophils]]"


==Overview==
*Another variant of leukocytosis is the [[leukemoid reaction]].
'''Leukocytosis''' is an elevation of the white blood cell count (the [[leukocyte]] count) above the normal range. The normal adult human leukocyte count in peripheral [[blood]] is 4.4-10.8 x 10<sup>9</sup>/[[litre|L]]. A white blood count of 11.0 x 10<sup>9</sup>/[[litre|L]] or more suggests leukocytosis. Often, the word refers to an increased [[neutrophil granulocyte]] count, as neutrophils are the main granulocytes.  An increase in [[eosinophil granulocyte]] is known as [[eosinophilia]]. Granulocytosis can be a feature of a number of disease processes including [[infection]], especially [[bacterium|bacteria]]; [[malignancy]], most notably [[leukemia]] (it is the main feature of [[chronic myelogenous leukemia]], CML) and [[autoimmune disease]].  Although it may be a sign of illness, leukocytosis in-and-of itself is not a disorder, nor is it a disease.  It is simply a laboratory finding.
*The image below demonstrates a graphic figure that illustrates [[hematopoietic]] growth factors in leukocytosis.<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>


==Epidemiology and Demographics==
[[Image:Hematopoietic growth factors.png|600px|center|thumb|Hematopoietic growth factors in leukocytosis, Courtesy of Wikipedia]]
Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids.  Leukocytosis can also be the first indication of [[neoplastic]] growth of leukocytes.


==Pathophysiology==
==Pathophysiology==
The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from [[bone marrow]] storage pools, decreased margination of leukocytes onto vessel walls, decreased [[leukocyte extravasation|extravasation]] of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.
*The pathogenesis of leukocytosis is characterized by:<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
:*An increased release of [[White blood cells|leukocytes]] from bone marrow storage pools
:*Decreased margination of leukocytes onto vessel walls
:*Decreased [[extravasation]] of leukocytes from the vessels into tissues
:*Increase in number of precursor cells in the [[bone marrow]]


==Classification Scheme==
==Causes==
Leukocytosis can be subcategorized by the type of white blood cell that is increased in number.


===Granulocytosis / Neutrophilia===
* '''To see a comprehensive list of all causes of leukocytosis, please click [[Leukocytosis causes|here]]'''
[[Granulocytosis]] or [[neutrophilia]] is a subcategory of leukocytosis in which [[neutrophil]] count is elevated.


'''''For complete list of conditions that cause neutrophilia, click [[Granulocytosis|here]]'''''
{| class="wikitable"
! colspan="5" | Causes of leukocytosis
|-
! Neutrophilic <br> leukocytosis <br> ([[neutrophilia]])
|
*Acute [[bacterial infection]]s, especially [[pyogenic infection]]s
*Sterile inflammation
** [[Tissue necrosis]]
***[[Myocardial infarction]]
***[[Burn]]s
|-
! Eosinophilic <br> leukocytosis <br>([[eosinophilia]])
|
*[[Allergy|Allergic]] disorders
**[[Asthma]]
**[[Hay fever]]
**[[Drug allergies]]
**[[Allergic skin disease]]s
***[[Pemphigus]]
***[[Dermatitis herpetiformis]]
*[[Parasitic infection]]s
*Some forms of [[malignancy]]
**[[Hodgkin's lymphoma]]
**Some forms of [[Non-Hodgkin lymphoma]]
*Systemic [[autoimmune|auto-immune]] diseases (e.g. [[systemic lupus erythematosus|SLE]])
*Some forms of [[vasculitis]]
*[[Cholesterol embolism]] (transiently)
|-
! Basophilic <br> leukocytosis <br> [[Basophilia]]
|
*[[Myeloproliferative disease]], e.g. [[Chronic myelogenous leukemia]]
|-
! [[Monocytosis]]
|
*[[Chronic infection]]s
**[[Tuberculosis]]
**[[Bacterial endocarditis]]
**[[Rickettsiosis]]
**[[Malaria]]
*[[Systemic autoimmune diseases]], e.g. [[systemic lupus erythematosus|SLE]]
*[[Inflammatory bowel disease]]s, e.g. [[ulcerative colitis]]
|-
! [[Lymphocytosis]]
|
*[[Chronic (medicine)|Chronic]] [[infection]]s
**[[Tuberculosis]]
**[[Brucellosis]]
*[[Viral infection]]s
**[[Hepatitis]]
**[[Cytomegalovirus]] infection
**[[Infectious mononucleosis]]
*[[Pertussis]]
*Some forms of [[malignancy]], such as [[lymphocytic leukemia|lymphocytic leukæmias]]
|}


===Eosinophilia===
==Epidemiology and Demographics==
[[Eosinophilia]] is a subcategory of leukocytosis in which [[eosinophil]] count is elevated.


'''''For complete list of conditions that cause eosinophilia, click [[Eosinophilia|here]]'''''
* Leukocytosis is very common.<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>


===Monocytosis===  
===Age===
[[Monocytosis]] is a subcategory of leukocytosis in which [[monocyte]] count is elevated.
*Patients of all age groups may develop leukocytosis.
*Normal [[White blood cell|white blood count]] differential changes with age.
*Leukocytosis in [[neonates]] is more common, in comparison to children and adults.<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
===Gender===
*Leukocytosis affects men and women equally.


'''''For complete list of conditions that cause monocytosis, click [[Monocytosis|here]]'''''
===Race===
*There is no racial predilection for leukocytosis.


===Lymphocytosis===  
==Risk Factors==
[[Lymphocytosis]] is a subcategory of leukocytosis in which [[lymphocyte]] count is elevated.
*Common risk factors in the development of leukocytosis include:<ref name="pmid11087187">{{cite journal |vauthors=Abramson N, Melton B |title=Leukocytosis: basics of clinical assessment |journal=Am Fam Physician |volume=62 |issue=9 |pages=2053–60 |year=2000 |pmid=11087187 |doi= |url=}}</ref>
:*Physiological processes (e.g. stress, exercise, [[pregnancy]])
:*Drugs (e.g. [[Corticosteroid|corticosteroids]], [[lithium]], [[Beta agonist|beta agonists]])
:*[[Physical trauma|Trauma]]
:*[[Stress (medicine)|Stress]]


'''''For complete list of conditions that cause neutrophilia, click [[Lymphocytosis|here]]'''''
== Natural History, Complications and Prognosis==
*The majority of patients with leukocytosis are initially symptomatic.<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>
*Early clinical features include:<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>
:*[[Fever]]
:*[[Hyperhidrosis]]
:*[[Fatigue]]
*Common complications of leukocytosis include:<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>
:*[[Tumor lysis syndrome]]
:*[[Disseminated intravascular coagulation|Disseminated intravascular coagulopathy]]
:*[[Respiratory failure|Acute respiratory failure]]
:*[[Pulmonary hemorrhage]]
:*CNS infarction
:*[[Splenic infarction]]
:*[[Myocardial ischemia]]
:*[[Renal failure]]
*Prognosis generally depends on the underlying etiologies.<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>


==Leukemoid Reaction==
== Diagnosis ==
A leukocyte count of above 25 to 30 x 10<sup>9</sup>/[[litre|L]] is termed as [[leukemoid reaction]]. This occurs as a reaction of healthy bone marrow to extreme stress, trauma, or infection.


[[Leukemoid reaction]] is different from [[leukemia]] and from leukoerythroblastosis, in which immature blood cells are present in peripheral blood.
=== Symptoms ===
*Leukocytosis is usually symptomatic.
*Symptoms of leukocytosis are often unspecific such as:<ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref>
:*Weight loss
:*Fevers of unknown origin
:*[[Hyperhidrosis]]
:*[[Chronic pain]]
:*[[Fatigue]]
:*[[Dyspnea]]
:*[[Malaise]]
*Obtain history of the following:
:*Clinical features
:*Duration (e.g. days, weeks, months)
:*Remainder of complete blood count


==Differential Diagnosis of Causes of {{PAGENAME}} (specifically)==
=== Laboratory Findings ===
===By Organ System===
*Laboratory findings that are consistent with the diagnosis of leukocytosis involve the <ref name="wiki">Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016 </ref> [[White blood cell count]] being above the normal range (greater than 11,000 per mm3).
{|height:100px" border="1"
==Differentiating Leukocytosis from Other Diseases==
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
Differential diagnosis methods of leukocytosis:
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | [No underlying causes
{|
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! colspan="4" rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Mechanism
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! colspan="11" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestations
! colspan="8" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para−clinical findings
! colspan="1" rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
! colspan="6" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
|-
! colspan="8" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
|-
|-
|-bgcolor="LightSteelBlue"
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
| '''Chemical / poisoning'''
! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Increased bone marrow production
|bgcolor="Beige"| No underlying causes
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! colspan="1" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |CBC
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
|-
|-
|-bgcolor="LightSteelBlue"
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous
| '''Dermatologic'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive
|bgcolor="Beige"| No underlying causes
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
|-
|-
|-bgcolor="LightSteelBlue"
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hematologic
| '''Drug Side Effect'''
! align="center" style="background:#DCDCDC;" |[[Granulocytosis|Hereditary neutrophilia]]<ref name="HerringSmith1974">{{cite journal|last1=Herring|first1=William Benjamin|last2=Smith|first2=Laurin Gresham|last3=Walker|first3=Richard Isley|last4=Herion|first4=John Carroll|title=Hereditary neutrophilia|journal=The American Journal of Medicine|volume=56|issue=5|year=1974|pages=729–734|issn=00029343|doi=10.1016/0002-9343(74)90642-1}}</ref>
|bgcolor="Beige"| [[Plerixafor]]          
| align="left" style="background:#F5F5F5;" + |
* Unknown
* Germline [[mutation]] in [[CSF3R]]
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |Rare [[Dominance relationship|autosomal dominant]] genetic disorder
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="center" style="background:#F5F5F5;" + |Normal
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + | −
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |
* Normal [[Granulocyte|granulocytes]]
* [[Histiocyte|Histiocytes]] of Gaucher type
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Molecular testing
| align="left" style="background:#F5F5F5;" + |
* High [[leukocyte alkaline phosphatase]]
* Progress to [[leukemia]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Myeloproliferative neoplasm|Myeloproliferative neoplasms]]<ref name="pmid20052751">{{cite journal |vauthors=Tefferi A |title=Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms-biologically plausible but clinically uncertain |journal=Am. J. Hematol. |volume=85 |issue=2 |pages=93–4 |date=February 2010 |pmid=20052751 |doi=10.1002/ajh.21614 |url=}}</ref>
| '''Ear Nose Throat'''
| align="center" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
*Unknown
|-  
*[[Mutation]]
|-bgcolor="LightSteelBlue"
| align="center" style="background:#F5F5F5;" + |−
| '''Endocrine'''
| align="center" style="background:#F5F5F5;" + | +
|bgcolor="Beige"| No underlying causes
| align="center" style="background:#F5F5F5;" + |−
|-
| align="center" style="background:#F5F5F5;" + |−
|-bgcolor="LightSteelBlue"
| align="center" style="background:#F5F5F5;" + | +
| '''Environmental'''
| align="center" style="background:#F5F5F5;" + | +
|bgcolor="Beige"| No underlying causes
| align="center" style="background:#F5F5F5;" + |Elderly
| align="left" style="background:#F5F5F5;" + |Exposure to:
*[[Chemotherapy]]
*[[Radiation therapy]]
*[[Tobacco smoking|Tobacco smoke]]
| align="left" style="background:#F5F5F5;" + |
* [[Petechia|Petechiae]]
* [[Purpura]]
* Diffuse erythematous [[rash]]
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑/↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑/↓
| align="left" style="background:#F5F5F5;" + |
*Large [[Platelet|platelets]]
*Ovalomacrocytosis
*Basophilic stippling
*[[Howell-Jolly body]]
*Pelger-Huet anomaly
*Ring [[Sideroblastic anemia|sideroblasts]]
| align="left" style="background:#F5F5F5;" + |
*Impaired [[myeloid]] maturation
*[[Congenital dyserythropoietic anemia|Dyserythropoiesis]]
*Dysgranulopoiesis
*Dysmegakaryocytopoiesis
*Hypercellular [[bone marrow]]
*[[Fibrosis]]
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Thrombosis]] at unusual sites
*[[Thrombosis]] in younger patients
*Might transformed to [[acute leukemia]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Polycythemia vera]]<ref name="pmid26336886">{{cite journal |vauthors=Boiocchi L, Gianelli U, Iurlo A, Fend F, Bonzheim I, Cattaneo D, Knowles DM, Orazi A |title=Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications |journal=Mod. Pathol. |volume=28 |issue=11 |pages=1448–57 |date=November 2015 |pmid=26336886 |doi=10.1038/modpathol.2015.100 |url=}}</ref>
| '''Gastroenterologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| [[Colonic diverticulitis]]
*Autonomous [[Red blood cell|erythrocyte]] production
*[[JAK2]] mutation (> 95%)
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Mean age > 60 years old
| align="left" style="background:#F5F5F5;" + |
*[[Stroke]]
*[[Visual system|Visual disturbance]]
| align="center" style="background:#F5F5F5;" + |
* Facial [[Hypervolemia|plethora]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*Painful [[erythema]]
| align="center" style="background:#F5F5F5;" + |Nl to ↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*Elevated normochromic, normocytic [[Red blood cell|RBCs]]
*[[Thrombocytosis]]
*≥ 10% immature myeloid precursors
*Leukoerythroblastic picture
| align="left" style="background:#F5F5F5;" + |
* Increased [[myeloid]]:[[Red blood cell|erythroid]] ratio due to granulocytic proliferation
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Stroke]]
*[[Venous thrombosis]]
*[[Myelofibrosis]]
*[[Acute leukemia]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Microangiopathic hemolytic anemia]] (MAHA)<ref name="pmid27288467">{{cite journal |vauthors=Morton JM, George JN |title=Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer |journal=J Oncol Pract |volume=12 |issue=6 |pages=523–30 |date=June 2016 |pmid=27288467 |doi=10.1200/JOP.2016.012096 |url=}}</ref>
| '''Genetic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| [[Interleukin 1 receptor antagonist|Interleukin 1 receptor antagonist deficiency]]
* [[Microvascular disease|Microangiopathy]]
* [[Leukemoid reaction]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Coagulopathy|Bleeding disorder]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Fragmented [[Red blood cell|RBCs]]
* [[Red blood cell|Schistocytes]]
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] + clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* Non-immune [[hemolysis]]
* Elevated [[Lactate dehydrogenase|LDH]]
* Elevated [[alkaline phosphatase]]
* Negative [[Coombs test|direct Coomb's test]]
* [[Thrombosis]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |Leukoerythroblastosis<ref name="pmid25562031">{{cite journal |vauthors=Canbolat Ayhan A, Timur C, Ayhan Y, Kes G |title=Leukoerythroblastosis Mimicking Leukemia: A case report |journal=Iran J Pediatr |volume=24 |issue=3 |pages=332–3 |date=June 2014 |pmid=25562031 |pmc=4276592 |doi= |url=}}</ref>
| '''Hematologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes 
* Space-occupying lesions in the [[bone marrow]]
* [[Infection]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Coagulopathy|Bleeding disorder]]
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Satiety|Early satiety]]
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
* Nucleated red cells
* [[Reticulocyte|Reticulocytosis]]
* [[Poikilocytosis|Poikilocytes]]
* Circulating immature [[White blood cells|white cells]], generally [[Myelocyte|myelocytes]] and [[Promyelocyte|promyelocytes]]
| align="left" style="background:#F5F5F5;" + |
* Circulating immature [[White blood cells|white cells]], generally [[Myelocyte|myelocytes]] and [[Promyelocyte|promyelocytes]]
* [[Myelofibrosis]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination|Bone marrow biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow|Marrow]] infiltrative disorders
* [[Physical trauma|Trauma]]
* [[Sepsis|Septicemia]]
* Massive [[hemolysis]]
* [[Macrocytic anemia|Megaloblastic anemia]]
* [[Hematopoiesis|Extramedullary hematopoiesis]]
|-
|-
|-bgcolor="LightSteelBlue"
! rowspan="12" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Immunology/
| '''Iatrogenic'''
Rheumatology
|bgcolor="Beige"| No underlying causes
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Leukocyte adhesion deficiency]]<ref name="pmid26434744">{{cite journal |vauthors=Levy-Mendelovich S, Rechavi E, Abuzaitoun O, Vernitsky H, Simon AJ, Lev A, Somech R |title=Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1 |journal=Immunol. Res. |volume=64 |issue=2 |pages=476–82 |date=April 2016 |pmid=26434744 |doi=10.1007/s12026-015-8706-5 |url=}}</ref>
| '''Infectious Disease'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes         
* [[Primary immunodeficiency]]
* Failure to express [[CD18]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare [[autosomal recessive]], [[Leukocyte adhesion deficiency|LAD]] II more in Middle East and Brazil
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* Characteristic facial appearance, short stature, limb malformations, and severe [[Developmental disability|developmental delay]] in [[Leukocyte adhesion deficiency|LAD]] II
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Signs of different [[Infection|infections]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Flow cytometry]]
| align="left" style="background:#F5F5F5;" + |
* Recurrent [[Infection|bacterial infections]]
* Delay in [[umbilical cord]] sloughing
* Inability to form [[Abscess|abscesses]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |Cryopyrin-associated periodic syndromes<ref name="pmid30035647">{{cite journal |vauthors=Labrousse M, Kevorkian-Verguet C, Boursier G, Rowczenio D, Maurier F, Lazaro E, Aggarwal M, Lemelle I, Mura T, Belot A, Touitou I, Sarrabay G |title=Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review |journal=Crit Rev Clin Lab Sci |volume=55 |issue=6 |pages=432–442 |date=September 2018 |pmid=30035647 |doi=10.1080/10408363.2018.1488805 |url=}}</ref>
| '''Musculoskeletal / Ortho'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* Unknown
* [[Mutation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |[[Dominance relationship|Autosomal dominant]] autoinflammatory syndrome
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Urticaria|Hive]]-like [[rash]] without [[Itch|itching]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Red eyes
* [[Nausea and vomiting|Vomiting]]
* [[Headache]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Genetic testing|Genetic tests]]
| align="left" style="background:#F5F5F5;" + |
* [[Blindness]]
* [[Hearing impairment|Hearing loss]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Rheumatoid arthritis]]<ref name="pmid20870100">{{cite journal |vauthors=Scott DL, Wolfe F, Huizinga TW |title=Rheumatoid arthritis |journal=Lancet |volume=376 |issue=9746 |pages=1094–108 |date=September 2010 |pmid=20870100 |doi=10.1016/S0140-6736(10)60826-4 |url=}}</ref><ref name="pmid24568138">{{cite journal |vauthors=Glant TT, Mikecz K, Rauch TA |title=Epigenetics in the pathogenesis of rheumatoid arthritis |journal=BMC Med |volume=12 |issue= |pages=35 |date=February 2014 |pmid=24568138 |pmc=3936819 |doi=10.1186/1741-7015-12-35 |url=}}</ref>
| '''Neurologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any, more in young women, between 30-60 years old
| align="left" style="background:#F5F5F5;" + |
* Positive family history
* [[Smoking|Cigarette smoking]]
* [[Obesity]]
| align="left" style="background:#F5F5F5;" + |
* Deformed [[Joint|joints]]
* [[Rheumatoid nodule|Rheumatoid nodules]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Weight loss]]
* [[Fatigue]]
* [[Dry eyes]] and mouth
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + positive [[Anti-citrullinated protein antibody|anti-CCP antibodies]]
| align="left" style="background:#F5F5F5;" + |
* [[Osteoporosis]]
* [[Infection|Infections]]
* [[Carpal tunnel syndrome]]
* Multi-organ involvement
* [[Lymphoma]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Juvenile rheumatoid arthritis|Juvenile onset rheumatoid arthritis]]<ref name="pmid23763801">{{cite journal |vauthors=Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, Ahmad TM |title=Juvenile rheumatoid arthritis |journal=J Coll Physicians Surg Pak |volume=23 |issue=6 |pages=409–12 |date=June 2013 |pmid=23763801 |doi=06.2013/JCPSP.409412 |url=}}</ref>
| '''Nutritional / Metabolic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Children under the age of 16
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
*Blotchy [[rash]] on a child's arms and legs
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Dry eyes]] and mouth
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + laboratory findings
| align="left" style="background:#F5F5F5;" + |
* [[Uveitis]]
* [[Infection|Infections]]
* Multi-organ involvement
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Still's disease|Adult Still's disease]]<ref name="pmid25613167">{{cite journal |vauthors=Kadavath S, Efthimiou P |title=Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options |journal=Ann. Med. |volume=47 |issue=1 |pages=6–14 |date=February 2015 |pmid=25613167 |doi=10.3109/07853890.2014.971052 |url=}}</ref>
| '''Obstetric/Gynecologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Rare [[autoimmune disease]]
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* Nonpruritic salmon-colored [[rash]] (usually over [[trunk]] or [[Limb (anatomy)|extremities]] while [[Fever|febrile]])
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Headache]]
* [[Pharyngitis|Sore throat]]
* [[Weight loss]]
* [[Muscle pain]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnosis of exclusion
| align="left" style="background:#F5F5F5;" + |
* High [[ferritin]]
* Negative [[Antinuclear antibodies|ANA]]
* [[Meningitis|Aseptic meningitis]]
*[[Sensorineural hearing loss]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Kawasaki disease]]<ref name="pmid25399940">{{cite journal |vauthors=Sundel RP |title=Kawasaki disease |journal=Rheum. Dis. Clin. North Am. |volume=41 |issue=1 |pages=63–73, viii |date=2015 |pmid=25399940 |doi=10.1016/j.rdc.2014.09.010 |url=}}</ref>
| '''Oncologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in Asian ethnicity boys
| align="center" style="background:#F5F5F5;" + |NA
| align="left" style="background:#F5F5F5;" + |
* Diffuse [[maculopapular]] erythematous [[rash]] in the [[Sex organ|genital]] area, and red [[Eye|eyes]], [[Lip (disambiguation)|lips]], [[Hand|palms]] or [[Sole (foot)|soles]] of the feet
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Strawberry [[tongue]]
* [[Pharyngitis|Sore throat]]
* [[Diarrhea]]
* Bilateral [[Conjunctiva|conjunctival]] inflammation
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnostic criteria
| align="left" style="background:#F5F5F5;" + |
* Medium-sized-vessel [[vasculitis]]
* [[Coronary artery aneurysm]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Inflammatory bowel disease|IBD]]<ref name="pmid24415861">{{cite journal |vauthors=Zhang YZ, Li YY |title=Inflammatory bowel disease: pathogenesis |journal=World J. Gastroenterol. |volume=20 |issue=1 |pages=91–9 |date=January 2014 |pmid=24415861 |pmc=3886036 |doi=10.3748/wjg.v20.i1.91 |url=}}</ref>
| '''Opthalmologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
* [[Mutation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in young
| align="left" style="background:#F5F5F5;" + |
* [[Stress (medicine)|Stress]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Pyoderma gangrenosum]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Nausea and vomiting|Vomiting]]
* [[Diarrhea]]
* [[Rectal bleeding]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Colonoscopy]] and [[biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Primary sclerosing cholangitis]]
* [[Euthyroid sick syndrome|Non-thyroidal illness syndrome]]
* [[Deep vein thrombosis|DVT]]
* [[Cryptogenic organizing pneumonia|Bronchiolitis obliterans organizing pneumonia]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Sarcoidosis]]<ref name="pmid25473783">{{cite journal |vauthors=Modaresi Esfeh J, Culver D, Plesec T, John B |title=Clinical presentation and protocol for management of hepatic sarcoidosis |journal=Expert Rev Gastroenterol Hepatol |volume=9 |issue=3 |pages=349–58 |date=March 2015 |pmid=25473783 |doi=10.1586/17474124.2015.958468 |url=}}</ref>
| '''Overdose / Toxicity'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune-]]<nowiki/>mediated
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Autoimmune disease]], more in young African American women
| align="left" style="background:#F5F5F5;" + |
* Positive family history
| align="left" style="background:#F5F5F5;" + |
* [[Rash|Rashes]]
* [[Erythema nodosum]]
* [[Granuloma annulare]]
* [[Lupus pernio]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
Bilateral [[Hilar lymphadenopathy|hilar adenopathy]]
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Weight loss]]
* [[Blurred vision|Blurry vision]]
* [[Dyspnea|Shortness of breath]]
* [[Cough]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnosis of exclusion
| align="left" style="background:#F5F5F5;" + |
* [[Interstitial lung disease]]
* Systemic [[Inflammation|inflammatory]] disease
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Hepatitis|Chronic hepatitis]]<ref name="pmid26092643">{{cite journal |vauthors=Gish RG, Given BD, Lai CL, Locarnini SA, Lau JY, Lewis DL, Schluep T |title=Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities |journal=Antiviral Res. |volume=121 |issue= |pages=47–58 |date=September 2015 |pmid=26092643 |doi=10.1016/j.antiviral.2015.06.008 |url=}}</ref>
| '''Psychiatric'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Infection]]
* [[Autoimmunity|Autoimmune]]
* [[Ischemia|Ischemic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Elderly
| align="left" style="background:#F5F5F5;" + |
* [[Alcoholism|Alcohol use]]
* Acute [[infection]]
| align="left" style="background:#F5F5F5;" + |
* [[Jaundice]]
* [[Ascites]] and [[peripheral edema]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Weight loss]]
* [[Nausea and vomiting]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Liver biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Hirsutism]]
* [[Amenorrhea]]
* [[Coagulopathy]]
* [[Hepatic encephalopathy]]
* [[Esophageal varices]]
* [[Hepatorenal syndrome]]
* [[Liver mass|Liver cancer]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Sweet's syndrome|Sweet syndrome]]<ref name="pmid30247226">{{cite journal |vauthors=Das A, Burmeister R, Chhaya R, Eisenga B, Kumar A |title=Sweet Syndrome in a Patient With Systemic Lupus Erythematosus |journal=J Clin Rheumatol |volume= |issue= |pages= |date=September 2018 |pmid=30247226 |doi=10.1097/RHU.0000000000000904 |url=}}</ref>
| '''Pulmonary'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* [[Immunity (medical)|Immune]]-mediated
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Rare
| align="left" style="background:#F5F5F5;" + |
* [[Relapse]] and [[Remission (medicine)|remission]]
| align="left" style="background:#F5F5F5;" + |
* [[Tenderness (medicine)|Tender]], red, well-demarcated [[Papule|papules]] and [[Plaque|plaques]] on the [[head]], [[neck]], [[Leg|legs]], and arms
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Conjunctivitis]]
* [[Iridocyclitis]]
* [[Aphthous ulcer|Oral aphthae]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="left" style="background:#F5F5F5;" + |
* Papillary and mid-dermal mixed infiltrate of [[Neutrophil|polymorphonuclear]] leukocytes with nuclear fragmentation and [[Histiocytic|histiocytic cells]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Diagnostic criteria
| align="left" style="background:#F5F5F5;" + |
* Cutaneous marker of systemic disease
* [[Acute myeloid leukemia|Acute myelogenous leukemia]]
* Immunologic disease
* Slight increase in [[alkaline phosphatase]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Gout|Acute gout]]<ref name="pmid24334652">{{cite journal |vauthors=Dalbeth N, Zhong CS, Grainger R, Khanna D, Khanna PP, Singh JA, McQueen FM, Taylor WJ |title=Outcome measures in acute gout: a systematic literature review |journal=J. Rheumatol. |volume=41 |issue=3 |pages=558–68 |date=March 2014 |pmid=24334652 |pmc=4217650 |doi=10.3899/jrheum.131244 |url=}}</ref>
| '''Renal / Electrolyte'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* Elevated levels of [[uric acid]] in the [[blood]]
* [[Diet (nutrition)|Diet]]
* [[Genetics|Genetic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Older males
| align="left" style="background:#F5F5F5;" + |
* [[Alcoholism|Alcohol use]]
* Acute [[infection]]
| align="left" style="background:#F5F5F5;" + |
* [[Tophus|Tophi]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* Leukocytosis
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* [[Arthritis]]
* Urate [[nephropathy]]
|-
|-
|-bgcolor="LightSteelBlue"
! rowspan="6" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Medication
| '''Rheum / Immune / Allergy'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
|bgcolor="Beige"| No underlying causes       
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Steroid]]<ref name="pmid7304648">{{cite journal |vauthors=Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J |title=Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis |journal=Am. J. Med. |volume=71 |issue=5 |pages=773–8 |date=November 1981 |pmid=7304648 |doi= |url=}}</ref>
| '''Sexual'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* Release of [[Granulocyte|granulocytes]] from the [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Steroid]] use
* [[Autoimmune disease]]
* [[Cancer|Malignancy]]
| align="center" style="background:#F5F5F5;" + |
* [[Obesity|Obese]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Abdominal pain]]
* [[Muscle weakness]]
* [[Growth failure]]
* [[Pubertal delay]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
* Large numbers of microspherocytes
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Thrombosis|Thromboembolic]]<nowiki/>complications
* [[Cushing's syndrome|Cushing syndrome]]
* [[Diabetes mellitus]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Filgrastim]] (Myeloid growth factor)<ref name="pmid24142827">{{cite journal |vauthors=Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, Cataland SR, Heaney ML, Hudock S, Kloth DD, Kuter DJ, Lyman GH, McMahon B, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Steensma DP, Talbott M, Vadhan-Raj S, Westervelt P, Westmoreland M, Dwyer M, Ho M |title=Myeloid growth factors |journal=J Natl Compr Canc Netw |volume=11 |issue=10 |pages=1266–90 |date=October 2013 |pmid=24142827 |doi= |url=}}</ref>
| '''Trauma'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* Release of [[Granulocyte|granulocytes]] from the [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Cancer|Malignancy]]
* [[Neutropenia]]
| align="left" style="background:#F5F5F5;" + |
* [[Alopecia|Hair loss]]
* Local skin reactions at the site of [[Injection (medicine)|injection]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Cough]]
* [[Chest pain]]
* [[Nausea and vomiting|Vomiting]]
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Alveolus|Alveolar]] hemorrhage
* [[Acute respiratory distress syndrome]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Lithium]]<ref name="pmid25735990">{{cite journal |vauthors=Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schön S, Svedlund J |title=Effects of 10 to 30 years of lithium treatment on kidney function |journal=J. Psychopharmacol. (Oxford) |volume=29 |issue=5 |pages=608–14 |date=May 2015 |pmid=25735990 |doi=10.1177/0269881115573808 |url=}}</ref>
| '''Urologic'''
| align="left" style="background:#F5F5F5;" + |
|bgcolor="Beige"| No underlying causes
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Bipolar disorder]]
| align="left" style="background:#F5F5F5;" + |
* [[Weight gain]]
* [[Acne vulgaris|Acne]]
* Hand [[tremor]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Confusion]]
* [[Constipation]] or [[diarrhea]]
* Decreased [[memory]]
* [[Xerostomia|Dry mouth]]
* [[Muscle weakness]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Extrapyramidal system|Extrapyramidal side effects]]
* [[Goitre|Euthyroid goitre]]
* [[Hypothyroidism]]
* [[Renal insufficiency|Kidney damage]]
|-
|-
|-bgcolor="LightSteelBlue"
! align="center" style="background:#DCDCDC;" |[[Catecholamine|Catecholamines]]
| '''Miscellaneous'''
([[epinephrine]])<ref name="pmid12417430">{{cite journal |vauthors=Bedoui S, Lechner S, Gebhardt T, Nave H, Beck-Sickinger AG, Straub RH, Pabst R, von Hörsten S |title=NPY modulates epinephrine-induced leukocytosis via Y-1 and Y-5 receptor activation in vivo: sympathetic co-transmission during leukocyte mobilization |journal=J. Neuroimmunol. |volume=132 |issue=1-2 |pages=25–33 |date=November 2002 |pmid=12417430 |doi= |url=}}</ref>
|bgcolor="Beige"| [[Neuroleptic malignant syndrome]]
| align="left" style="background:#F5F5F5;" + |
* Stimulation of [[bone marrow]] myelopoiesis
* Egress into the circulation
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Anaphylaxis]]
* [[Respiratory disease|Respiratory diseases]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
* [[Diaphoresis|Diaphoretic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dizziness]]
* [[Tremor]]
* [[Anxiety]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Thrombosis|Thromboembolic]]<nowiki/>complications
|-
|-
! align="center" style="background:#DCDCDC;" |[[Tretinoin|ATRA]]<ref name="pmid17257495">{{cite journal |vauthors=Bi KH, Jiang GS |title=Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide |journal=Cell. Mol. Immunol. |volume=3 |issue=6 |pages=421–7 |date=December 2006 |pmid=17257495 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Differentiating [[Promyelocyte|promyelocytes]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Acne vulgaris|Acne]]
* [[Acute promyelocytic leukemia]]
| align="left" style="background:#F5F5F5;" + |
* [[Xeroderma|Skin dryness]]
* [[Alopecia|Hair loss]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dyspnea|Shortness of breath]]
* [[Headache]]
* [[Paresthesia|Numbness]]
* [[Depression]]
* [[Itch|Itchiness]]
* [[Nausea and vomiting|Vomiting]]
* [[Myalgia|Muscle pain]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + history of drug consumption
| align="left" style="background:#F5F5F5;" + |
* [[Teratology|Teratogen]]
* [[Thrombosis]]
* [[Idiopathic intracranial hypertension|Benign intracranial hypertension]]
* [[Hyperlipoproteinemia|Hypercholesterolemia]]
* [[Liver|Liver damage]]
|-
! rowspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Infection|Infections]]<ref name="pmid24012414">{{cite journal |vauthors=Horasan ES, Dağ A, Ersoz G, Kaya A |title=Surgical site infections and mortality in elderly patients |journal=Med Mal Infect |volume=43 |issue=10 |pages=417–22 |date=October 2013 |pmid=24012414 |doi=10.1016/j.medmal.2013.07.009 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |
* [[Infection]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* Close contact
* [[Immunodeficiency]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="left" style="background:#F5F5F5;" + |
* [[Fatigue]]
* [[Nausea and vomiting]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation+ culture
| align="left" style="background:#F5F5F5;" + |
* Depends on etiology
|-
! align="center" style="background:#DCDCDC;" |[[Allergy]]<ref name="pmid29871797">{{cite journal |vauthors=Davis MDP, van der Hilst JCH |title=Mimickers of Urticaria: Urticarial Vasculitis and Autoinflammatory Diseases |journal=J Allergy Clin Immunol Pract |volume=6 |issue=4 |pages=1162–1170 |date=2018 |pmid=29871797 |doi=10.1016/j.jaip.2018.05.006 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
* Activation of [[chloride]] transport
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Anaphylaxis]]
* [[Respiratory|Respiratory diseases]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
* [[Diaphoresis|Diaphoretic]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dizziness]]
* [[Tremor]]
* [[Anxiety]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Myelofibrosis|Megakaryocytic]]<nowiki/>fragments
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |Post [[splenectomy]]<ref name="pmid29766137">{{cite journal |vauthors=Bilello JF, Sharp VL, Dirks RC, Kaups KL, Davis JW |title=After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma |journal=Trauma Surg Acute Care Open |volume=3 |issue=1 |pages=e000159 |date=2018 |pmid=29766137 |pmc=5887792 |doi=10.1136/tsaco-2017-000159 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* Prior surgical removal of the [[spleen]]
* [[Sickle-cell disease|Sickle cell disease]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
* Incidental laboratory finding
* [[Thrombosis]]
|-
! align="center" style="background:#DCDCDC;" |[[Smoking|Cigarette smoking]]<ref name="pmid27688691">{{cite journal |vauthors=Lymperaki E, Makedou K, Iliadis S, Vagdatli E |title=Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers |journal=Hippokratia |volume=19 |issue=4 |pages=293–7 |date=2015 |pmid=27688691 |pmc=5033137 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Reduced [[Blood plasma|plasma]] volume
* Accelerated [[erythropoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Smoking|Cigarette smoking]]
| align="left" style="background:#F5F5F5;" + |
* [[Cyanosis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Cough]]
* [[Dyspnea]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Stress (medicine)|Stress]]/[[Physical exercise|exercise]]<ref name="pmid26477922">{{cite journal |vauthors=Simpson RJ, Kunz H, Agha N, Graff R |title=Exercise and the Regulation of Immune Functions |journal=Prog Mol Biol Transl Sci |volume=135 |issue= |pages=355–80 |date=2015 |pmid=26477922 |doi=10.1016/bs.pmbts.2015.08.001 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Reduced plasma volume
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Athlete
| align="left" style="background:#F5F5F5;" + |
* [[Physical exercise|Exercise]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Howell-Jolly body|Howell-Jolly bodies]]
* Nucleated [[Red blood cell|RBCs]]
| align="left" style="background:#F5F5F5;" + |
* Proliferation of [[Megakaryocyte|megakaryocytes]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Infant|Infancy]]<ref name="pmid26580401">{{cite journal |vauthors=Nouatin O, Gbédandé K, Ibitokou S, Vianou B, Houngbegnon P, Ezinmegnon S, Borgella S, Akplogan C, Cottrell G, Varani S, Massougbodji A, Moutairou K, Troye-Blomberg M, Deloron P, Luty AJ, Fievet N |title=Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum |journal=PLoS ONE |volume=10 |issue=11 |pages=e0139606 |date=2015 |pmid=26580401 |pmc=4651557 |doi=10.1371/journal.pone.0139606 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Physiologic
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Infant|Infancy]]
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Pregnancy]]<ref name="pmid26621538">{{cite journal |vauthors=Perseghin P |title=Erythrocyte exchange and leukapheresis in pregnancy |journal=Transfus. Apher. Sci. |volume=53 |issue=3 |pages=279–82 |date=December 2015 |pmid=26621538 |doi=10.1016/j.transci.2015.11.007 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Physiologic
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Pregnancy]]
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Platelet]] clumping<ref name="pmid25369589">{{cite journal |vauthors=Castrillo A, Álvarez I, Tolksdorf F |title=In vitro evaluation of platelet concentrates suspended in additive solution and treated for pathogen reduction: effects of clumping formation |journal=Blood Transfus |volume=13 |issue=2 |pages=281–6 |date=April 2015 |pmid=25369589 |pmc=4385077 |doi=10.2450/2014.0162-14 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Spurious
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Cytoplasm|Cytoplasmic]] fragments
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="center" style="background:#F5F5F5;" + |−
|-
! align="center" style="background:#DCDCDC;" |[[Cryoglobulinemia|Mixed cryoglobulinemia]]<ref name="pmid25837517">{{cite journal |vauthors=Cacoub P, Comarmond C, Domont F, Savey L, Saadoun D |title=Cryoglobulinemia Vasculitis |journal=Am. J. Med. |volume=128 |issue=9 |pages=950–5 |date=September 2015 |pmid=25837517 |doi=10.1016/j.amjmed.2015.02.017 |url=}}</ref>
| align="center" style="background:#F5F5F5;" + |Spurious
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Cancer|Malignancy]]
* [[Autoimmune disease]]
* [[Infection]]
| align="left" style="background:#F5F5F5;" + |
* Atypical cutaneous [[Ulcer|ulcers]]
* Palpable [[purpura]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Headache]]
* [[Confusion]]
* Blurry or loss of [[Visual system|vision]]
* Generalized [[Muscle weakness|weakness]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
* [[Cytoplasm|Cytoplasmic]] fragments
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Skin biopsy]]
| align="left" style="background:#F5F5F5;" + |
* [[Vasculitis]]
* [[Neuropathy]]
* [[Raynaud's phenomenon|Raynaud phenomenon]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physiologic
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Autonomous increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Reactive increased bone marrow production
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demargination of peripheral blood neutrophils
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Abdominal pain
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Asplenia
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hepatosplenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lymphadenopathy
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Joint involvement
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |ESR/CRP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BUN/Cr
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |LFT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|}
|}
===In alphabetical order<ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>===
*[[Colonic diverticulitis]]
*[[Interleukin 1 receptor antagonist|Interleukin 1 receptor antagonist deficiency]]
*[[Neuroleptic malignant syndrome]]
*[[Plerixafor]]
==Related Chapters==
*[[Granulocytosis]]
*[[Neutrophilia]]
*[[Eosinophilia]]
*[[Monocytosis]]
*[[Lymphocytosis]]


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{Hematology}}
{{Lymphatic disease}}


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Lakshmi Gopalakrishnan, M.B.B.S. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Synonyms and keywords: Elevated white blood cell count; Right-shift leukocytosis; Left-shift leukocytosis

Overview

Leukocytosis is the elevation of the white blood cell count above the normal range (greater than 11,000 per mm3). Leukocytosis is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections, bone tumors, strenuous exercise, emotional stress, pregnancy, anesthesia, and epinephrine administration. Leukocytosis may be classified into 5 sub-types: neutrophilia (most common), lymphocytosis, monocytosis, eosinophilia, and basophilia. Other classifications include: Left shift or right shift leukocytosis. The pathogenesis of leukocytosis is characterized by the increase of leukocytes (primarily neutrophils), followed by the proliferation and release of granulocyte and monocyte precursors in the bone marrow, which is then stimulated by several products of inflammation including C3a and G-CSF.[1]

Historical Perspective

  • Leukocytosis was first discovered by Paul Kautchakoff in 1846.[1]

Classification

  • Leukocytosis may be classified into 5 sub-types:[2]
  • Leukocytosis may also be classified into 2 groups:[2]
  • Left shift (most common)
  • Immature leukocytes increase
  • Proliferation and release of granulocyte and monocyte precursors in the bone marrow
  • Usually stimulated by several products of inflammation including C3a and G-CSF
  • Right shift
  • Another variant of leukocytosis is the leukemoid reaction.
  • The image below demonstrates a graphic figure that illustrates hematopoietic growth factors in leukocytosis.[3]
Hematopoietic growth factors in leukocytosis, Courtesy of Wikipedia

Pathophysiology

  • The pathogenesis of leukocytosis is characterized by:[2]
  • An increased release of leukocytes from bone marrow storage pools
  • Decreased margination of leukocytes onto vessel walls
  • Decreased extravasation of leukocytes from the vessels into tissues
  • Increase in number of precursor cells in the bone marrow

Causes

  • To see a comprehensive list of all causes of leukocytosis, please click here
Causes of leukocytosis
Neutrophilic
leukocytosis
(neutrophilia)
Eosinophilic
leukocytosis
(eosinophilia)
Basophilic
leukocytosis
Basophilia
Monocytosis
Lymphocytosis

Epidemiology and Demographics

  • Leukocytosis is very common.[2]

Age

  • Patients of all age groups may develop leukocytosis.
  • Normal white blood count differential changes with age.
  • Leukocytosis in neonates is more common, in comparison to children and adults.[2]

Gender

  • Leukocytosis affects men and women equally.

Race

  • There is no racial predilection for leukocytosis.

Risk Factors

  • Common risk factors in the development of leukocytosis include:[2]

Natural History, Complications and Prognosis

  • The majority of patients with leukocytosis are initially symptomatic.[3]
  • Early clinical features include:[3]
  • Common complications of leukocytosis include:[3]
  • Prognosis generally depends on the underlying etiologies.[3]

Diagnosis

Symptoms

  • Leukocytosis is usually symptomatic.
  • Symptoms of leukocytosis are often unspecific such as:[3]
  • Obtain history of the following:
  • Clinical features
  • Duration (e.g. days, weeks, months)
  • Remainder of complete blood count

Laboratory Findings

  • Laboratory findings that are consistent with the diagnosis of leukocytosis involve the [3] White blood cell count being above the normal range (greater than 11,000 per mm3).

Differentiating Leukocytosis from Other Diseases

Differential diagnosis methods of leukocytosis:

Category Condition Etiology Mechanism Congenital Acquried Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs
Lab Findings
Physiologic Increased bone marrow production Demargination of peripheral blood neutrophils Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other CBC PBS Bone marrow exam ESR/CRP BUN/Cr LFT
Autonomous Reactive WBC HB Plt
Hematologic Hereditary neutrophilia[4] + + Rare autosomal dominant genetic disorder
  • Positive family history
Normal Nl + Nl Nl Nl Nl Nl Nl Molecular testing
Myeloproliferative neoplasms[5] + + + Elderly Exposure to: ± + Nl + ↑/↓ ↑/↓ Nl Nl Bone marrow examination + clinical manifestation
Polycythemia vera[6] + + Mean age > 60 years old + + Nl to ↑
  • Elevated normochromic, normocytic RBCs
  • Thrombocytosis
  • ≥ 10% immature myeloid precursors
  • Leukoerythroblastic picture
Nl Nl Nl Bone marrow examination + clinical manifestation
Microangiopathic hemolytic anemia (MAHA)[7] + + + Any + + + NA Bone marrow examination + clinical manifestation
Leukoerythroblastosis[8] + + Any + Nl + Nl Bone marrow biopsy
Immunology/

Rheumatology

Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Leukocyte adhesion deficiency[9] + + Rare autosomal recessive, LAD II more in Middle East and Brazil
  • Positive family history
+ Nl ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Nl Nl Flow cytometry
Cryopyrin-associated periodic syndromes[10] + + Autosomal dominant autoinflammatory syndrome
  • Positive family history
+ Nl + ↓/↑
  • Leukocytosis
  • Leukocytosis
Nl Genetic tests
Rheumatoid arthritis[11][12] + + Any, more in young women, between 30-60 years old + Nl +
  • Leukocytosis
NA Nl Nl Clinical manifestation + positive anti-CCP antibodies
Juvenile onset rheumatoid arthritis[13] + + Children under the age of 16
  • Positive family history
  • Blotchy rash on a child's arms and legs
+ Nl + +
  • Leukocytosis
NA Nl Nl Clinical manifestation + laboratory findings
Adult Still's disease[14] + + Rare autoimmune disease NA + Nl + +
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Kawasaki disease[15] + + Autoimmune disease, more in Asian ethnicity boys NA + + Nl + +
  • Leukocytosis
NA Nl Nl Diagnostic criteria
IBD[16] + + Autoimmune disease, more in young
  • Stress
  • Positive family history
+ + Nl + + +
  • Leukocytosis
NA Nl Nl Colonoscopy and biopsy
Sarcoidosis[17] + + Autoimmune disease, more in young African American women
  • Positive family history
+ + Nl + +

Bilateral hilar adenopathy

+
  • Leukocytosis
NA Nl Nl Diagnosis of exclusion
Chronic hepatitis[18] + + Elderly + + + + +
  • Leukocytosis
NA Liver biopsy
Sweet syndrome[19] + + Rare + + Nl + +
  • Leukocytosis
Nl Nl Diagnostic criteria
Acute gout[20] + + Older males + +
  • Leukocytosis
NA Nl Clinical manifestation
Medication Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Steroid[21] + + + Any + Nl to ↓ Nl to ↓ Nl Clinical manifestation + history of drug consumption
Filgrastim (Myeloid growth factor)[22] + + + Any + Nl to ↓ + Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Lithium[23]
  • Unknown
+ + + Any Nl Nl to ↓ NA NA Nl Nl Clinical manifestation + history of drug consumption
Catecholamines

(epinephrine)[24]

  • Stimulation of bone marrow myelopoiesis
  • Egress into the circulation
+ + + Any Nl to ↓ Nl Nl Clinical manifestation + history of drug consumption
ATRA[25] + + + Any Nl Nl Nl NA NA Nl Clinical manifestation + history of drug consumption
Other Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings
Infections[26] + + + + Any
  • Acutely ill
+ + Nl to ↓ ± ± ± Nl Nl Clinical manifestation+ culture
  • Depends on etiology
Allergy[27]
  • Unknown
  • Activation of chloride transport
+ + + + Any Nl to ↓ Nl Nl Clinical manifestation
Post splenectomy[28]
  • Unknown
+ + + Any
  • Normal
± Nl + Nl Nl Clinical manifestation
Cigarette smoking[29] + + + Any Nl NA NA Nl Nl Nl Clinical manifestation
Stress/exercise[30]
  • Reduced plasma volume
+ + + Athlete
  • Normal
Nl Nl Nl Clinical manifestation
Infancy[31] Physiologic + + Infancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Pregnancy[32] Physiologic + + Pregnancy
  • Normal
Nl NA NA Nl Nl Nl Clinical manifestation
Platelet clumping[33] Spurious + Any
  • Normal
Nl Nl Nl Nl Nl Nl Clinical manifestation
Mixed cryoglobulinemia[34] Spurious + Any Nl + Nl to ↓ Nl Nl Nl Nl Skin biopsy
Category Condition Etiology Physiologic Autonomous increased bone marrow production Reactive increased bone marrow production Demargination of peripheral blood neutrophils Congenital Acquried Demography History Appearance Fever Abdominal pain BP Asplenia Hepatosplenomegaly Lymphadenopathy Joint involvement Other signs WBC HB Plt PBS Bone marrow exam ESR/CRP BUN/Cr LFT Gold standard Associated findings

References

  1. 1.0 1.1 Chabot-Richards DS, George TI (2014). "Leukocytosis". Int J Lab Hematol. 36 (3): 279–88. doi:10.1111/ijlh.12212. PMID 24750674.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Abramson N, Melton B (2000). "Leukocytosis: basics of clinical assessment". Am Fam Physician. 62 (9): 2053–60. PMID 11087187.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
  4. Herring, William Benjamin; Smith, Laurin Gresham; Walker, Richard Isley; Herion, John Carroll (1974). "Hereditary neutrophilia". The American Journal of Medicine. 56 (5): 729–734. doi:10.1016/0002-9343(74)90642-1. ISSN 0002-9343.
  5. Tefferi A (February 2010). "Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms-biologically plausible but clinically uncertain". Am. J. Hematol. 85 (2): 93–4. doi:10.1002/ajh.21614. PMID 20052751.
  6. Boiocchi L, Gianelli U, Iurlo A, Fend F, Bonzheim I, Cattaneo D, Knowles DM, Orazi A (November 2015). "Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications". Mod. Pathol. 28 (11): 1448–57. doi:10.1038/modpathol.2015.100. PMID 26336886.
  7. Morton JM, George JN (June 2016). "Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer". J Oncol Pract. 12 (6): 523–30. doi:10.1200/JOP.2016.012096. PMID 27288467.
  8. Canbolat Ayhan A, Timur C, Ayhan Y, Kes G (June 2014). "Leukoerythroblastosis Mimicking Leukemia: A case report". Iran J Pediatr. 24 (3): 332–3. PMC 4276592. PMID 25562031.
  9. Levy-Mendelovich S, Rechavi E, Abuzaitoun O, Vernitsky H, Simon AJ, Lev A, Somech R (April 2016). "Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion deficiency type 1". Immunol. Res. 64 (2): 476–82. doi:10.1007/s12026-015-8706-5. PMID 26434744.
  10. Labrousse M, Kevorkian-Verguet C, Boursier G, Rowczenio D, Maurier F, Lazaro E, Aggarwal M, Lemelle I, Mura T, Belot A, Touitou I, Sarrabay G (September 2018). "Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review". Crit Rev Clin Lab Sci. 55 (6): 432–442. doi:10.1080/10408363.2018.1488805. PMID 30035647.
  11. Scott DL, Wolfe F, Huizinga TW (September 2010). "Rheumatoid arthritis". Lancet. 376 (9746): 1094–108. doi:10.1016/S0140-6736(10)60826-4. PMID 20870100.
  12. Glant TT, Mikecz K, Rauch TA (February 2014). "Epigenetics in the pathogenesis of rheumatoid arthritis". BMC Med. 12: 35. doi:10.1186/1741-7015-12-35. PMC 3936819. PMID 24568138.
  13. Naz S, Mushtaq A, Rehman S, Bari A, Maqsud A, Khan MZ, Ahmad TM (June 2013). "Juvenile rheumatoid arthritis". J Coll Physicians Surg Pak. 23 (6): 409–12. doi:06.2013/JCPSP.409412 Check |doi= value (help). PMID 23763801.
  14. Kadavath S, Efthimiou P (February 2015). "Adult-onset Still's disease-pathogenesis, clinical manifestations, and new treatment options". Ann. Med. 47 (1): 6–14. doi:10.3109/07853890.2014.971052. PMID 25613167.
  15. Sundel RP (2015). "Kawasaki disease". Rheum. Dis. Clin. North Am. 41 (1): 63–73, viii. doi:10.1016/j.rdc.2014.09.010. PMID 25399940.
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