Leukocytosis

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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]

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

Overview

Leukocytosis is an 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 subtypes: neutrophilia (most common), lymphocytosis, monocytosis, eosinophilia, and basophilia. Other classification, include: Left shift or right shift leucocytosis. 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 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 subtypes:^[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

Reduced count or lack of "young neutrophils"
Associated with the presence of "giant neutrophils

Other 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 marrow

Causes

To see a comprehensive list of all causes of leukocytosis, please click here

Causes of leukocytosis
Neutrophilic leukocytosis (neutrophilia)	Acute bacterial infections, especially pyogenic infections Sterile inflammation Tissue necrosis Myocardial infarction Burns
Eosinophilic leukocytosis (eosinophilia)	Allergic disorders Asthma Hay fever Drug allergies Allergic skin diseases Pemphigus Dermatitis herpetiformis Parasitic infections Some forms of malignancy Hodgkin's lymphoma Some forms of Non-Hodgkin lymphoma Systemic autoimmune diseases (e.g. SLE) Some forms of vasculitis Cholesterol embolism (transiently)
Basophilic leukocytosis Basophilia	Myeloproliferative disease, e.g. Chronic myelogenous leukemia
Monocytosis	Chronic infections Tuberculosis Bacterial endocarditis Rickettsiosis Malaria Systemic autoimmune diseases, e.g. SLE Inflammatory bowel diseases, e.g. ulcerative colitis
Lymphocytosis	Chronic infections Tuberculosis Brucellosis Viral infections Hepatitis Cytomegalovirus infection Infectious mononucleosis Pertussis Some forms of malignancy, such as lymphocytic leukæmias

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, compared 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]

Physiologic processes (eg, stress, exercise, pregnancy)
Drugs (e.g.corticosteroids, lithium, beta agonists)
Trauma
Stress

Natural History, Complications and Prognosis

The majority of patients with leukocytosis are initially symptomatic.^[3]
Early clinical features, include:^[3]

Fever
Hyperhidrosis
Fatigue

Common complications of leukocytosis, include:^[3]

Tumor lysis syndrome
Disseminated intravascular coagulopathy
Acute respiratory failure
Pulmonary hemorrhage
CNS infarction
Splenic infarction
Myocardial ischemia
Renal failure

Prognosis is generally depends on the underlying etiologies.^[3]

Diagnosis

Symptoms

Leukocytosis is usually symptomatic.
Symptoms of leukocytosis are often unspecific, such as:^[3]

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

Laboratory Findings

Laboratory findings consistent with the diagnosis of leukocytosis, include:^[3]

White blood cell count above the normal range

Greater than 11,000 per mm3

Differentiating Leukocytosis from Other Diseases

Category	Condition	Etiology	Mechanism				Congenital	Acquried	Clinical manifestations											Para−clinical findings								Gold standard	Associated findings
									Demography	History	Symptoms			Signs						Para−clinical findings
											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
			Physiologic	Autonomous	Reactive	Demargination of peripheral blood neutrophils					Appearance	Fever	Abdominal pain	BP	Asplenia	Hepatosplenomegaly	Lymphadenopathy	Joint involvement	Other	WBC	HB	Plt	PBS	Bone marrow exam	ESR/CRP	BUN/Cr	LFT
Hematologic	Hereditary neutrophilia^[4]	Unknown Germline mutation in CSF3R	−	+	−	−	+	−	Rare autosomal dominant genetic disorder	Positive family history	Normal	−	−	Nl	−	+	−	−	−	↑	Nl	Nl	Normal granulocytes Histiocytes of Gaucher type	Nl	Nl	Nl	Nl	Molecular testing	High leukocyte alkaline phosphatase Progress to leukemia
	Myeloproliferative neoplasms^[5]	Unknown Mutation	−	+	−	−	+	+	Elderly	Exposure to Chemotherapy Radiation therapy Tobacco smoke	Petechiae Purpura Diffuse erythematous rash	±	+	Nl	−	+	−	−	Shortness of breath Fatigue	↑/↓	↓	↑/↓	Large platelets Ovalomacrocytosis Basophilic stippling Howell-Jolly body Pelger-Huet anomaly Ring sideroblasts	Impaired myeloid maturation Dyserythropoiesis Dysgranulopoiesis Dysmegakaryocytopoiesis Hypercellular bone marrow Fibrosis	↑	Nl	Nl	Bone marrow examination + clinical manifestation	Thrombosis at unusual sites Thrombosis in younger patients Might transformed to acute leukemia
	Polycythemia vera^[6]	Autonomous erythrocyte production JAK2 mutation (> 95%)	−	+	−	−	+	−	Mean age >60 years old	Stroke Visual disturbance	Facial plethora	−	−	↑	−	+	+	−	Painful erythema	Nl to ↑	↑	↑	Elevated normochromic, normocytic RBCs Thrombocytosis ≥ 10% immature myeloid precursors Leukoerythroblastic picture	Increased myeloid:erythroid ratio due to granulocytic proliferation	Nl	Nl	Nl	Bone marrow examination + clinical manifestation	Stroke Venous thrombosis Myelofibrosis Acute leukemia
	Microangiopathic hemolytic anemia (MAHA)^[7]	Microangiopathy Leukemoid reaction	−	+	−	−	+	+	Any	Bleeding disorder Positive family history	Pallor	+	+	↓	−	+	−	−	Shortness of breath Fatigue	↑	↓	↑	Fragmented RBCs Schistocytes	NA	↑	↑	↑	Bone marrow examination + clinical manifestation	Non-immune hemolysis Elevated LDH Elevated alkaline phosphatase Negative direct Coomb's test Thrombosis
	Leukoerythroblastosis^[8]	Space-occupying lesions in the bone marrow Infection	−	+	−	−	−	+	Any	Bleeding disorder	Pallor	−	+	Nl	−	+	−	−	Early satiety Fatigue	↑	↓	↓	Nucleated red cells Reticulocytosis Poikilocytes Circulating immature white cells, generally myelocytes and promyelocytes	Circulating immature white cells, generally myelocytes and promyelocytes Myelofibrosis	↑	Nl	↑	Bone marrow biopsy	Marrow infiltrative disorders Trauma Septicemia Massive hemolysis Megaloblastic anemia Extramedullary hematopoiesis
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]	Primary immunodeficiency Failure to express CD18	−	+	−	−	+	−	Rare autosomal recessive, LAD II more in Middle East and Brazil	Positive family history	Characteristic facial appearance, short stature, limb malformations, and severe developmental delay in LAD II	+	−	Nl	−	−	−	−	Signs of different infections	↑	↓	↓/↑	Leukocytosis	Leukocytosis	Nl	Nl	Nl	Flow cytometry	Recurrent bacterial infections Delay in umbilical cord sloughing Inability to form abscesses
	Cryopyrin-associated periodic syndromes^[10]	Unknown Mutation	−	+	−	−	+	−	Autosomal dominant autoinflammatory syndrome	Positive family history	Hive-like rash without itching	+	−	Nl	−	−	−	+	Red eyes Vomiting Headache	↑	↓	↓/↑	Leukocytosis	Leukocytosis	↑	Nl	↑	Genetic tests	Blindness Hearing loss
	Rheumatoid arthritis^[11]^[12]	Immune mediated	−	+	−	−	−	+	Any, more in young women, between 30-60 years old	Positive family history Cigarette smoking Obesity	Deformed joints Rheumatoid nodules	+	−	Nl	−	−	−	+	Weight loss Fatigue Dry eyes and mouth	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Clinical manifestation + positive anti-CCP antibodies	Osteoporosis Infections Carpal tunnel syndrome Multi-organ involvement Lymphoma
	Juvenile onset rheumatoid arthritis^[13]	Immune mediated	−	+	−	−	−	+	Children under the age of 16	Positive family history	Blotchy rash on a child's arms and legs	+	−	Nl	−	−	+	+	Fatigue Dry eyes and mouth	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Clinical manifestation + laboratory findings	Uveitis Infections Multi-organ involvement
	Adult Still's disease	Immune mediated	−	+	−	−	−	+	Rare autoimmune disease	NA	Nonpruritic salmon-colored rash (usually over trunk or extremities while febrile)	+	−	Nl	−	−	+	+	Headache Sore throat Weight loss Muscle pain	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Diagnosis of exclusion	High ferritin Negative ANA Aseptic meningitis Sensorineural hearing loss
	Kawasaki disease	Immune mediated	−	+	−	−	−	+	Autoimmune disease, more in Asian ethnicity boys	NA	Diffuse macular-papular erythematous rash in the genital area, and red eyes, lips, palms or soles of the feet	+	+	Nl	−	−	+	+	Strawberry tongue Sore throat Diarrhea Bilateral conjunctival inflammation	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Diagnostic criteria	Medium-sized-vessel vasculitis Coronary artery aneurysm
	IBD	Immune mediated Mutation	−	+	−	−	−	+	Autoimmune disease, more in young	Stress Positive family history	Pyoderma gangrenosum	+	+	Nl	−	+	+	+	Vomiting Diarrhea Rectal bleeding	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Colonoscopy and biopsy	Primary sclerosing cholangitis Non-thyroidal illness syndrome DVT Bronchiolitis obliterans organizing pneumonia
	Sarcoidosis	Immune mediated Unknown	−	+	−	−	−	+	Autoimmune disease, more in young African American women	Positive family history	Rashes, noduli, erythema nodosum, granuloma annulare, lupus pernio	+	+	Nl	−	+	+ Bilateral hilar	+	Fatigue Weight loss Blurry vision Shortness of breath Cough	↑	↓	↑	Leukocytosis	NA	↑	Nl	Nl	Diagnosis of exclusion	Interstitial lung disease Systemic inflammatory disease
	Chronic hepatitis	Infection Autoimmune Ischemic	−	+	−	−	−	+	Elderly	Alcohol use Acute infection	Jaundice Ascites and peripheral edema	+	+	↓	−	+	+	+	Fatigue Weight loss Nausea and vomitting	↑	↓	↑	Leukocytosis	NA	↑	↑	↑	Liver biopsy	Hirsutism Amenorrhea Coagulopathy Hepatic encephalopathy Esophageal varices Hepatorenal syndrome Liver cancer
	Sweet syndrome	Immune mediated Unknown	−	+	−	−	−	+	Rare	Relapse and remission	Tender, red, well-demarcated papules and plaques on the head, neck, legs, and arms	+	+	Nl	−	−	+	+	Conjunctivitis Iridocyclitis Oral aphthae	↑	↓	↑	Leukocytosis	Papillary and mid-dermal mixed infiltrate of polymorphonuclear leukocytes with nuclear fragmentation and histiocytic cells	↑	Nl	Nl	Diagnostic criteria	Cutaneous marker of systemic disease Acute myelogenous leukemia Immunologic disease Slight increase in alkaline phosphatase
	Acute gout	Elevated levels of uric acid in the blood Diet Genetic	−	+	−	−	−	+	Older males	Alcohol use Acute infection	Tophi	+	−		−	−	−	+	Fatigue	↑	↓	↑	Leukocytosis	NA	↑	↑	Nl	Clinical manifestation	Arthritis Urate nephropathy
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	Release of granulocytes from the bone marrow	−	−	+	+	−	+	Elderly	Steroid use Autoimmune disease Malignancy	Obese	−	+	Nl to ↓	−	−	−	−	Abdominal pain Muscle weakness Growth failure Pubertal delay	↑	Nl to ↓	↑	Megakaryocyticfragments Large numbers of microspherocytes	Proliferation of megakaryocytes	↑	↑	Nl	Clinical manifestation + history of drug consumption	Thromboemboliccomplications Cushing syndrome Diabetes mellitus
	Myeloid growth factors
	Lithium
	Cytokines
	Catecholamines (epinephrine)	Stimulation of bone marrow myelopoiesis Egress into the circulation	−	−	+	+	−	+	Any	Anaphylaxis Respiratory diseases	Acutely ill Diaphoretic	−	−	Nl to ↓	−	−	−	−	Dizziness Tremor Anxiety Dyspnea	↑	↑	↑	Megakaryocyticfragments	Proliferation of megakaryocytes	↑	Nl	Nl	Clinical manifestation + history of drug consumption	Thromboemboliccomplications
	ATRA
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	Infection	-	+	+	+	-	+	Any
	Allergy	Unknown Activation of chloride transport							Any	Anaphylaxis Respiratory diseases	Acutely ill Diaphoretic	−	−	Nl to ↓	−	−	−	−	Dizziness Tremor Anxiety Dyspnea	↑	↑	↑	Megakaryocyticfragments	Proliferation of megakaryocytes	↑	Nl	Nl	Clinical manifestation	−
	Post splenectomy	Unknown	−	−	+	+	−	+	Any	Prior surgical removal of the spleen Sickle cell disease	Normal	±	−	Nl	+	−	−	−	−	↑	↓	↑	Howell-Jolly bodies Nucleated RBCs	Proliferation of megakaryocytes	↑	Nl	Nl	Clinical manifestation	Incidental laboratory finding Thrombosis
	Down syndrome
	Cigarette smoking
	Stress/exercise								Athlete	Exercise	Normal	−	−	Nl	−	−	−	−	−	↑	↑	↑	Howell-Jolly bodies Nucleated RBCs	Proliferation of megakaryocytes	↑	Nl	Nl	Clinical manifestation	−
	Infancy
	Pregnancy
	Platelet clumping	Spurious
	Mixed cryoglobulinemia	Spurious
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

Treatment

Medical Therapy

The treatment for leukocytosis will depend on the underlying condition.^[3]

References

↑ ^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.
↑ ^2.0 ^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.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

Template:WikiDoc Sources

[pmid24750674-1] 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.

[pmid11087187-2] 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.

[wiki-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Leukocytosis. Wikipedia. https://en.wikipedia.org/wiki/Leukocytosis Accessed on May 23, 2016

[HerringSmith1974-4] 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.

[pmid20052751-5] 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.

[pmid26336886-6] 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.

[pmid27288467-7] 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.

[pmid25562031-8] 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.

[pmid26434744-9] 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.

[pmid30035647-10] 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.

[pmid20870100-11] 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.

[pmid24568138-12] 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.

[pmid23763801-13] 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.

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