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In some cases, lymphocytopenia can be further classified according to which kind of lymphocytes are reduced. If all three kinds of lymphocytes are suppressed, then the term is used without further qualification.
- In T lymphocytopenia, there are too few T lymphocytes, but normal numbers of other lymphocytes. It causes, and manifests as, a T cell deficiency. This is usually caused by HIV infection (resulting in AIDS), but may be Idiopathic CD4+ lymphocytopenia (ICL), which is a very rare heterogeneous disorder defined by CD4+ T-cell counts below 300 cells/μL in the absence of any known immune deficiency condition, such as human immunodeficiency virus (HIV) infection or chemotherapy.
- In B lymphocytopenia, there are too few B lymphocytes, but possibly normal numbers of other lymphocytes. It causes, and manifests as, a humoral immune deficiency. This is usually caused by medications that suppress the immune system.
- In NK lymphocytopenia, there are too few natural killer cells, but normal numbers of other lymphocytes. This is very rare.
Lymphocytopenia, or lymphopenia, is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. The opposite is lymphocytosis, which refers to an excessive level of lymphocytes.
Lymphocytopenia may be present as part of a pancytopenia, when the total numbers of all types of blood cells are reduced.
A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen.
Lymphocytosis is an increase in the number of lymphocytes in the blood. In adults, lymphocytosis is present when the lymphocyte count is greater than 4000 per microliter (4.0 x 10(9)/L), in older children greater than 7000 per microliter and in infants greater than 9000 per microliter. Lymphocytes normally represent 20 to 40% of circulating white blood cells.
Lymphocytosis is usually detected when a complete blood count is obtained. If not provided the lymphocyte count can be calculated by multiplying the total white blood cell (WBC) count by the percentage of lymphocytes found in the differential count. The lymphocyte count can also be directly measured by flow cytometry.
An increase in the number of white blood cells in circulation is called leukocytosis. This increase is most commonly caused by inflammation. There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues. Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis.
Lymphocytosis is a feature of infection, particularly in children. In the elderly, lymphoproliferative disorders, including chronic lymphocytic leukaemia and lymphomas, often present with lymphadenopathy and a lymphocytosis.
Causes of absolute lymphocytosis include:
- acute viral infections, such as infectious mononucleosis (glandular fever), hepatitis and Cytomegalovirus infection
- other acute infections such as pertussis
- some protozoal infections, such as toxoplasmosis and American trypanosomiasis (Chagas disease)
- chronic intracellular bacterial infections such as tuberculosis or brucellosis
- chronic lymphocytic leukemia
- acute lymphoblastic leukemia
- lymphoma
- post-splenectomy state
- smoking
Causes of relative lymphocytosis include: age less than 2 years; acute viral infections; connective tissue diseases, thyrotoxicosis, Addison's disease, and splenomegaly with splenic sequestration of granulocytes.
A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (Phagocytes) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".
Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of dysfunction with their immune system are susceptible to develop a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders; however, there are also acquired and iatrogenic causes.
Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in people who have a compromised immune system. They are sometimes equated with "immunoproliferative disorders", but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.
The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. Lymphocytes can be identified by their large nucleus.
This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.
Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.
The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.
Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which neutrophils are elevated is neutrophilia; leukocytosis in which lymphocyte count is elevated is lymphocytosis; leukocytosis in which monocyte count is elevated is monocytosis; and leukocytosis in which eosinophil count is elevated is eosinophilia.
An extreme form of leukocytosis, in which the WBC count exceeds 100,000/µL, is leukostasis. In this form there are so many WBCs that clumps of them block blood flow. This leads to ischemic problems including transient ischemic attack and stroke.
Individuals with BENTA disease have polyclonal B cell lymphocytosis (i.e. excess B cells) developing in infancy, in addition to splenomegaly and lymphadenopathy. Patients may have low serum IgM and mildly anergic T cells. These features likely contribute to the mild immunodeficiency seen with BENTA disease. Patients are generally susceptible to recurrent sinopulmonary and ear infections in childhood, and may be more susceptible to certain viruses including Epstein-Barr virus, BK virus, and molluscum contagiosum.
Leukocytosis is white cells (the leukocyte count) above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections or bone tumors as well as leukemia. It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, and epinephrine administration.
There are five principle types of leukocytosis:
1. Neutrophilia (the most common form)
2. Lymphocytosis
3. Monocytosis
4. Eosinophilia
5. Basophilia
This increase in leukocyte (primarily neutrophils) is usually accompanied by a "left upper shift" in the ratio of immature to mature neutrophils and macrophages. The proportion of immature leukocytes decreases due to proliferation and inhibition of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF.
Although it may indicate illness, leukocytosis is considered a laboratory finding instead of a separate disease. This classification is similar to that of fever, which is also a test result instead of a disease.
"Right shift" in the ratio of immature to mature neutrophils is considered with reduced count or lack of "young neutrophils" (metamyelocytes, and band neutrophils) in blood smear, associated with the presence of "giant neutrophils". This fact shows suppression of bone marrow activity, as a hematological sign specific for pernicious anemia and radiation sickness.
A leukocyte count above 25 to 30 x 10/L is termed a "leukemoid reaction", which is the reaction of a healthy bone marrow to extreme stress, trauma, or infection. It is different from leukemia and from leukoerythroblastosis, in which either immature white blood cells (acute leukemia) or mature, yet non-functional, white blood cells (chronic leukemia) are present in peripheral blood.
BENTA disease is a rare genetic disorder of the immune system. BENTA stands for "B cell expansion with NF-κB and T cell anergy" and is caused by germline heterozygous gain-of-function mutations in the gene CARD11 (see OMIM entry #607210). This disorder is characterized by polyclonal B cell lymphocytosis with onset in infancy, splenomegaly, lymphadenopathy, mild immunodeficiency, and increased risk of lymphoma. Investigators Andrew L. Snow and Michael J. Lenardo at the National Institute of Allergy and Infectious Disease at the U.S. National Institutes of Health first characterized BENTA disease in 2012. Dr. Snow's current laboratory at the Uniformed Services University of the Health Sciences is now actively studying this disorder.
Diffuse infiltrative lymphocytosis syndrome occurs in HIV positive patients with low CD4 counts.
It is similar to Sjögren's syndrome, with painless parotid and submandibular swelling, and sicca symptoms.
The syndrome typically improves with HAART.
Monoclonal B-cell lymphocytosis (MBL) is a condition that resembles chronic lymphocytic leukemia (CLL), but does not meet the criteria for CLL, and does not require treatment. However, CLL requiring treatment develops at the rate of 1.1% per year.
The definition of CLL includes >5,000 CLL-phenotype B-cell lymphocytes per cubic millimeter. Patients with <5,000 (but not 0) CLL-phenotype B-cell lymphocytes per mm³, and no symptoms of CLL, are diagnosed with MBL.
The term monoclonal means that all the B cells are derived from a single cell.
Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously high blast cell count along with symptoms of decreased tissue perfusion. Leukostasis is associated with people who suffer from bone and blood disorders and is very common among people suffering from acute myeloid leukemia or chronic myeloid leukemia. Leukostasis is a pathlogic diagnosis that inhibits efficient flow to the microvasculature of the body. Continued and untreated leukostasis presents respiratory and neurological distress simultaneously and is a medical emergency, with untreated patient mortality rates reaching a minimum of 20 and a maximum of 40 percent.. A leukemia blood cell count greater than 50 x 10^9/ L ((50,000 / microL) or 100 x 10^9 L / (100,000/ microL) signifies hyperleuckocytosis. Symptoms of leukostasis start when blood levels of leukocytes reach over 100 x 10^9 / L (100,000 / microL). As stated before, these counts are critical and associated with Leukemias.
Using flow cytometry, monoclonal cells with cell surface markers similar to those in CLL can be detected in some healthy adults, who do not meet the criteria for CLL (i.e., >5,000 CLL-type lymphocytes per mm³). If the diagnosis of CLL is based on the B cell count rather than the total lymphocyte count (which includes both B and T cells), many patients formerly diagnosed with Rai Stage 0 CLL would instead be classified as having MBL.
Molecular techniques can detect monoclonal B cell levels as low as 3-5 B cells/microliter (comparable to the amount of stem cells in peripheral blood).
The term "monoclonal B-cell lymphocytosis" was proposed by a consensus committee in 2005 to indicate a monoclonal B cell population in a person with fewer than 5,000 B lymphocytes per microliter (or 5.0 x 10 B lymphocytes/L), no enlarged lymph nodes or enlarged liver and/or spleen or other indications of a lymphoproliferative disorder.
When a patient is suffering from symptomatic leuckocytosis, specifically caused by a form a leukemia, it is extremely common to find leukostasis in all their organs. The majority of the time a patient dies from neurological complications (40% of patients die due to neurological conditions) as opposed to particular organ damage. The lungs alone account for approximately 30 percent of leukostasis fatalities. All other organs combined attribute to 30 percent of deaths, with the major outliers being neurological and respiratory failure equating to 70 percent of all death rates. Damage to the microvasculature of the body is the primary cause of death by leukostasis. Microvasculatre damage to the lungs is only second to neurological damage because the body is already suffering from hypoxic conditions, which leads to lung tissue damage as the second leading cause of fatalities.
Pulmonary signs - Dyspnea and Hypoxia with or without diffuse interstitial or alveolar infiltrates on imaging studies.
Neurological signs - visual changes, headache, dizziness, tinnitus, gait instability, confusion, somnolence, coma.
The most common symptom is the patient is usually febrile, which is often linked with inflammation and possible infection.
Less common symptoms include electroencephalographic, signs of myocardial ischemia / right ventricular overload, increased renal insufficiency, priapism, acute limb ischemia and bowel infarction.
Chronic lymphoid leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on there is typically no symptoms. Latter non-painful lymph nodes swelling, feeling tired, fever, or weight loss for no clear reason may occur. Enlargement of the spleen and anemia may also occur. It typically worsens gradually.
Risk factors include having a family history of the disease. Agent Orange and certain insecticides might also be a risk. CLL results in the build up of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. It is divided into two main types those with a mutated IGHV gene and those without. Diagnosis is typically based on blood tests finding high numbers of mature lymphocytes and smudge cells.
Management of early disease is generally with watchful waiting. Infections should more readily be treated with antibiotics. In those with significant symptoms chemotherapy or immunotherapy may be used. The medications fludarabine, cyclophosphamide, and rituximab are typically the initial treatment in those who are otherwise healthy.
CLL affected about 904,000 people globally in 2015 and resulted in 60,700 deaths. The disease most common occurs in people over the age of 50. Males are affected more often than females. It is much less common in people from Asia. Five-year survival following diagnosis is approximately 83% in the United States. It represents less than 1% of deaths from cancer.
Lymphatic disease is a class of disorders which directly affect the components of the lymphatic system.
Examples include Castleman's disease and lymphedema.
Diseases and disorder
Hodgkin's Disease/Hodgkin's Lymphoma
This is a type of cancer of the lymphatic system. It can start almost anywhere in the body. It is believed to be caused by HIV, Epstein-Barr Syndrome, age and family history. Symptoms include weight loss, fever, swollen lymph nodes, night sweats, itchy skin, fatigue, chest pain, coughing or trouble swallowing.
Non-Hodgkin's Lymphoma
Lymphoma is a usually malignant cancer. It is caused by the body producing too many abnormal white blood cells. It is not the same as Hodgkin's Disease. Symptoms usually include painless, enlarged lymph node or nodes in the neck, weakness, fever, weight loss, and anemia.
Lymphadenitis is an infection of the lymph nodes usually caused by a virus, bacteria or fungi. Symptoms include redness or swelling around the lymph node.
Lymphangitis
Lymphangitis is an inflammation of the lymph vessels. Symptoms usually include swelling, redness, warmth, pain or red streaking around the affected area.
Lymphedema
Lymphedema is the chronic pooling of lymph fluid in the tissue. It usually starts in the feet or lower legs. It's also a side-effect of some surgical procedures.
Lymphocytosis
Lymphocytosis is a high lymphocyte count. It can be caused by an infection, blood cancer, lymphoma, or autoimmune disorders that are accompanied by chronic swelling.
Most people are diagnosed without symptoms as the result of a routine blood test that shows a high white blood cell count. Less commonly, CLL may present with enlarged lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma. In some individuals, the disease comes to light only after the cancerous cells overwhelm the bone marrow resulting in anemia producing tiredness or weakness.
Histology of the affected area commonly shows dense perivascular lymphocytic infiltration with reticulated degeneration of the epidermis. A study by Iwatsuki et al. detected Epstein-Barr virus (EBV) positive T-cells in the perivascular infiltration on biopsy in 28/29 patients tested. Antibody titers to EBV were measured in 14 of these patients and only five had abnormal antibody patterns consistent with chronic active EBV infection.