11/7/2017
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`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
`
`MMERCK(cid:98)MANUAL
`
`Professional / Hematology and Oncology / Leukopenias
`
`Lymphocytopenia
`
`Professional Version
`
`By Mary Territo, MD, Emeritus Professor of Medicine, Division of Hematology and Oncology,
`David Geffen School of Medicine at UCLA
`
`Lymphocytopenia is a total lymphocyte count of < 1000/μL in adults or < 3000/μL in children < 2 yr. Sequelae include
`opportunistic infections and an increased risk of malignant and autoimmune disorders. If the CBC reveals lymphocytopenia,
`testing for immunodeficiency and analysis of lymphocyte subpopulations should follow. Treatment is directed at the underlying
`disorder.
`
`The normal lymphocyte count in adults is 1000 to 4800/μL; in children < 2 yr, 3000 to 9500/μL. At age 6 yr, the lower limit of
`normal is 1500/μL.
`
`Both B and T cells are present in the peripheral blood; about 75% of the lymphocytes are T cells and 25% B cells. Because
`lymphocytes account for only 20 to 40% of the total WBC count, lymphocytopenia may go unnoticed when WBC count is checked
`without a differential.
`
`Clinical Calculator: Absolute Lymphocyte Count
`
`Almost 65% of blood T cells are CD4+ (helper) T cells. 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/μL (range, 300 to
`1300/μL), and the average number of cells of the other major T-cell subgroup, CD8+ (suppressor) T cells, is 600/μL (range, 100 to
`900/μL).
`
`Etiology
`
`Lymphocytopenia can be
`
`http://www.merckmanuals.com/professional/hematology-and-oncology/leukopenias/lymphocytopenia
`
`1/5
`
`Apotex v. Novartis
`IPR2017-00854
`NOVARTIS 2054
`
`
`
`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
`
`MMERCK(cid:98)MANUAL
`
`Professional / Hematology and Oncology / Leukopenias
`
`Lymphocytopenia
`
`Professional Version
`
`By Mary Territo, MD, Emeritus Professor of Medicine, Division of Hematology and Oncology,
`David Geffen School of Medicine at UCLA
`
`Lymphocytopenia is a total lymphocyte count of < 1000/μL in adults or < 3000/μL in children < 2 yr. Sequelae include
`opportunistic infections and an increased risk of malignant and autoimmune disorders. If the CBC reveals lymphocytopenia,
`testing for immunodeficiency and analysis of lymphocyte subpopulations should follow. Treatment is directed at the underlying
`disorder.
`
`The normal lymphocyte count in adults is 1000 to 4800/μL; in children < 2 yr, 3000 to 9500/μL. At age 6 yr, the lower limit of
`normal is 1500/μL.
`
`Both B and T cells are present in the peripheral blood; about 75% of the lymphocytes are T cells and 25% B cells. Because
`lymphocytes account for only 20 to 40% of the total WBC count, lymphocytopenia may go unnoticed when WBC count is checked
`without a differential.
`
`Clinical Calculator: Absolute Lymphocyte Count
`
`Almost 65% of blood T cells are CD4+ (helper) T cells. 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/μL (range, 300 to
`1300/μL), and the average number of cells of the other major T-cell subgroup, CD8+ (suppressor) T cells, is 600/μL (range, 100 to
`900/μL).
`
`Etiology
`
`Lymphocytopenia can be
`
`http://www.merckmanuals.com/professional/hematology-and-oncology/leukopenias/lymphocytopenia
`
`1/5
`
`Apotex v. Novartis
`IPR2017-00854
`NOVARTIS 2054
`
`
`
`11/7/2017
`
`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
`
`Acquired
`
`Inherited
`
`Acquired lymphocytopenia
`
`Acquired lymphocytopenia can occur with a number of other disorders (see Table: Causes of Lymphocytopenia). The most
`common causes include
`
`Protein-energy undernutrition
`
`AIDS and certain other viral infections
`
`Protein-energy undernutrition is the most common cause worldwide.
`
`AIDS is the most common infectious disease causing 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.
`
`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. Glucocorticoids can induce lymphocyte destruction.
`
`Lymphocytopenia may occur with lymphomas, autoimmune diseases such as SLE, rheumatoid arthritis, myasthenia gravis, and
`protein-losing enteropathy.
`
`Inherited lymphocytopenia
`
`Inherited lymphocytopenia (see Table: Causes of Lymphocytopenia) most commonly occurs in
`
`Severe combined immunodeficiency disorder
`
`Wiskott-Aldrich syndrome
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`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
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`It may occur with inherited immunodeficiency disorders and disorders that involve impaired lymphocyte production. Other
`inherited disorders, such as Wiskott-Aldrich syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase
`deficiency, may involve accelerated T-cell destruction. In many disorders, antibody production is also deficient.
`
`Causes of Lymphocytopenia
`
`Mechanism Examples
`
`AIDS
`
`Other infectious disorders, including hepatitis, influenza, TB, typhoid fever, and sepsis
`
`Dietary deficiency in patients with ethanol abuse, protein-energy undernutrition, or zinc deficiency
`
`Acquired
`
`Protein losing enteropathy
`
`Iatrogenic after use of cytotoxic chemotherapy, glucocorticoids, high-dose psoralen and ultraviolet A radiation therapy, lymphocyte antibody
`therapy, immunosuppressants, radiation therapy, or thoracic duct drainage
`
`Systemic disorders with autoimmune features (eg, aplastic anemia, Hodgkin lymphoma, myasthenia gravis, protein-losing enteropathy, RA, chronic
`kidney disease, sarcoidosis, SLE, thermal injury)
`
`Aplasia of lymphopoietic stem cells
`
`Ataxia-telangiectasia
`
`Cartilage-hair hypoplasia syndrome
`
`Hereditary
`
`Idiopathic CD4+ T lymphocytopenia
`
`Immunodeficiency with thymoma
`
`Severe combined immunodeficiency associated with a defect in the IL-2 receptor gamma-chain, deficiency of ADA or PNP, or an unknown defect
`
`Wiskott-Aldrich syndrome
`
`ADA =adenosine deaminase; PNP = purine nucleoside phosphorylase.
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`Symptoms and Signs
`
`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
`
`Lymphocytopenia per se generally causes no symptoms. However, findings of an associated disorder may include
`
`Absent or diminished tonsils or lymph nodes, indicative of cellular immunodeficiency
`
`Skin abnormalities (eg, alopecia, eczema, pyoderma, telangiectasia)
`
`Evidence of hematologic disease (eg, pallor, petechiae, jaundice, mouth ulcers)
`
`Generalized lymphadenopathy and splenomegaly, which may suggest HIV infection or Hodgkin lymphoma
`
`Lymphocytopenic patients experience recurrent infections or develop infections with unusual organisms. Pneumocystis jirovecii,
`cytomegalovirus, rubeola, and varicella pneumonias often are fatal. Lymphocytopenia is also a risk factor for the development of
`cancers and for autoimmune disorders.
`
`Diagnosis
`
`Clinical suspicion (repeated or unusual infections)
`
`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, even if initial screening tests are normal.
`
`Treatment
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`Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition
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`Treatment of associated infections
`
`Treatment of underlying disorder
`
`Sometimes IV 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 immune globulin is indicated if patients have chronic IgG deficiency, lymphocytopenia, and recurrent
`infections. Hematopoietic stem cell transplantation can be considered for all patients with congenital immunodeficiencies and
`may be curative.
`
`Key Points
`
`Lymphocytopenia is most often due to AIDS 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 immune globulin or, in patients with congenital
`immunodeficiency, stem cell transplantation is helpful.
`
`Last full review/revision November 2016 by Mary Territo, MD
`
`© 2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
`
`http://www.merckmanuals.com/professional/hematology-and-oncology/leukopenias/lymphocytopenia
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`5/5
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