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Lymphocytopenia

By

Mary Territo

, MD, David Geffen School of Medicine at UCLA

Last full review/revision Aug 2021| Content last modified Aug 2021
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Lymphocytopenia is a total lymphocyte count of < 1000/mcL ( < 1 × 109/L) in adults or < 3000/mcL (< 3 × 109/L) in children < 2 years. Sequelae include opportunistic infections and an increased risk of malignant and autoimmune disorders. If the complete blood count reveals lymphocytopenia, testing for immunodeficiency and analysis of lymphocyte subpopulations should follow. Treatment is directed at the underlying disorder.

Lymphocytes Lymphocytes The immune system consists of cellular components and molecular components that work together to destroy antigens. (See also Overview of the Immune System.) Although some antigens (Ags) can... read more are components of the cellular immune system and include T cells, B cells,and natural killer (NK) cells, all of which are present in the peripheral blood; about 75% of the lymphocytes are T cells, 20% B cells, and 5% NK cells. Because lymphocytes account for only 20 to 40% of the total white blood cell (WBC) count, lymphocytopenia may go unnoticed when the WBC count is checked without a differential.

The normal lymphocyte count in adults is 1000 to 4800/mcL (1 to 4.8 × 109/L; in children < 2 years, the normal count is 3000 to 9500/mcL (3 to 9.5 × 109/L). At age 6 years, the lower limit of normal is 1500/mcL (1.5 × 109/L). Different laboratories may have slightly different normal values.

Almost 65% of blood T cells are CD4+ (helper) T cells. Thus, most patients with lymphocytopenia have a reduced absolute number of T cells, particularly in the number of CD4+ T cells. The average number of CD4+ T cells in adult blood is 1100/mcL (range, 300 to 1300/mcL [1.1 × 109/L with a range of 0.3 to 1.3 × 109/L]), and the average number of cells of the other major T-cell subgroup, CD8+ (suppressor) T cells, is 600/mcL (range, 100 to 900/mcL).

Deficiencies of particular subsets of lymphocytes (eg, CD4+, CD8+, B, NK cells) may not be reflected in the lymphocyte count in the blood but may result in a functional lymphocytopenia. It is also important to note that the lymphocytes in the blood represent only a small proportion of the total lymphocyte pool and may not always correlate with the composition and numbers of lymphocytes in other lymphoid (eg, nodes, spleen) and non-lymphoid (eg, lung, liver) tissues.

Etiology of Lymphocytopenia

Lymphocytopenia can be

  • Acquired

  • Inherited

Acquired lymphocytopenia

The most common causes include

  • Protein-energy undernutrition

  • AIDS

  • COVID-19

  • Certain other viral infections

Protein-energy undernutrition is the most common cause worldwide.

AIDS Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more Human Immunodeficiency Virus (HIV) Infection patients routinely have lymphocytopenia, which arises from destruction of CD4+ T cells infected with HIV. Lymphocytopenia may also reflect impaired lymphocyte production arising from destruction of thymic or lymphoid architecture. In acute viremia due to HIV or other viruses, lymphocytes may undergo accelerated destruction from active infections with the virus, may be trapped in the spleen or lymph nodes, or may migrate to the respiratory tract.

Patients with COVID-19 COVID-19 COVID-19 is an acute, sometimes severe, respiratory illness caused by a novel coronavirus SARS-CoV-2. COVID-19 was first reported in late 2019 in Wuhan, China and has since spread extensively... read more also frequently have lymphocytopenia (35 to 83% of patients). Lower lymphocyte counts portend a poor prognosis and an increased likelihood of requiring ICU admission and of dying from the disease. The cause of the lymphocytopenia is not completely understood, but COVID-19 can directly infect lymphocytes, and a cytokine-related apoptosis of the cells is likely.

Iatrogenic lymphocytopenia is caused by cytotoxic chemotherapy, radiation therapy, or the administration of antilymphocyte globulin (or other lymphocyte antibodies). Long-term treatment for psoriasis using psoralen and ultraviolet A irradiation may destroy T cells. Long-term glucocorticoid therapy can induce lymphocyte destruction.

Inherited lymphocytopenia

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Symptoms and Signs of Lymphocytopenia

Lymphocytopenia per se generally causes no symptoms. However, findings of an associated disorder may include

Diagnosis of Lymphocytopenia

  • Clinical suspicion (repeated or unusual infections)

  • Complete blood count (CBC) with differential

  • Measurement of lymphocyte subpopulations and immunoglobulin levels

Lymphocytopenia is suspected in patients with recurrent viral, fungal, or parasitic infections but is usually detected incidentally on a CBC. P. jirovecii, cytomegalovirus, rubeola, or varicella pneumonias with lymphocytopenia suggest immunodeficiency.

Lymphocyte subpopulations are measured in patients with lymphocytopenia. Measurement of immunoglobulin levels should also be done to evaluate antibody production. Patients with a history of recurrent infections undergo complete laboratory evaluation for immunodeficiency Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more , even if initial screening tests are normal.

Treatment of Lymphocytopenia

  • Treatment of associated infections

  • Treatment of underlying disorder

  • Sometimes IV or subcutaneous immune globulin

  • Possibly hematopoietic stem cell transplantation

In acquired lymphocytopenias, lymphocytopenia usually remits with removal of the underlying factor or successful treatment of the underlying disorder. IV or subcutaneous immune globulin is indicated if patients have chronic immunoglobulin G deficiency, lymphocytopenia, and recurrent infections. Hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers (leukemias, lymphomas, myeloma) and other hematologic disorders... read more can be considered for all patients with congenital immunodeficiencies and may be curative.

Avoid giving live vaccines (because of the risk of causing infection) in these patients. Inactive or recombinant vaccines are safe, but their efficacy is variable depending on type and severity of the lymphocytopenia.

Key Points

  • Lymphocytopenia is most often due to AIDS, and recently COVID-19, or undernutrition, but it also may be inherited or caused by various infections, drugs, or autoimmune disorders.

  • Patients have recurrent viral, fungal, or parasitic infections.

  • Lymphocyte subpopulations and immunoglobulin levels should be measured.

  • Treatment is usually directed at the cause, but occasionally, IV or subcutaneous immune globulin or, in patients with congenital immunodeficiency, stem cell transplantation is helpful.

  • Avoid giving live vaccines in these patients.

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