Reactive Lymphocytosis In Common Disease States

It is normal for young children between the ages of 1 and 4 to have a relative lymphocytosis. The white cell differential in this age group will show a reversal in the number of lymphocytes to segmented neutrophils from the adult reference range. The lymphocytes, however, will have normal morphology (Fig. 10.11). By far the most common disease entity displaying variation in lymphocytes is infectious mononucleosis. This is viral illness caused by the Epstein-Barr virus (EBV), a member of the human herpes virus family, type 4. Although young children may become infected with EBV, the virus has a peak incidence at around 20 years of age. Most adults have been exposed to EBV by midlife, and this is recognized by demonstratable antibody production whether or not they have had an active case of infectious mononucleosis. The virus is found in body fluids, especially saliva, and is frequently passed through exchanges such as kissing, sharing food utensils, or drinking cups. The virus, which incubates for 3 to 4 weeks, enters through the oral passages and infects B lymphocytes. Normal lymphocytes become infected and are transformed into "reactive" (old terminology, "atypical") lymphocytes. Symptoms include sore throat, fatigue, anorexia, fever, and headache. The lymph nodes are usually always enlarged and there may be hepatosplenomegaly. Most individuals have a self-limited course of disease, which is uncomfortable but uncomplicated. Autoimmune hemolytic anemia and elevated liver enzymes may be a complication in less than 1% of patients.

Differential diagnosis includes careful examination of the peripheral smear, the results of rapid agglutination tests, and more sophisticated procedures such as ELISA or indirect immunofluorescence, which track

Lymphocytosis Photo
Figure 10.11 Normal lymphocyte.

EBV antigen positivity and measure IgG titers in convalescence. The peripheral smear is particularly impressive and usually shows a reactive lymphocytosis, with between 10% and 60% reactive lymphocytes (Fig. 10.12). Morphologically, these lymphocytes are larger than the normal large lymphocytes with an abundant royal blue cytoplasm, sometimes scalloping the red cells. They are easily identified with clumped chromatin material and must be recorded separately (on the differential counter) from the other nonreactive normal lymphocytes seen in the smear (Table 10.4). At times, the diagnosis of infectious mononucleosis is difficult to make in the event that the rapid agglutination test is negative, which it is in 10% of cases.11 The clinician should rely on symptoms, peripheral smear, and professional experience in pronouncing the disease. Molecular diagnostics is highly accurate but is expensive and a specialized procedure. There is no treatment for infectious mononucleosis except for bed rest and treatment of additional symptoms or possible subsequent infections.

Other Sources of Reactive Lymphocytosis

In most cases, viral disorders affect the CBC in a similar pattern. Most have an increased white count with a depressed number of segmented neutrophils and an increased lymphocyte count. Conditions such as cytomegalovirus and hepatitis A, B, and C viruses may show reactive lymphocytes of a morphology similar to infectious mononucleosis. Cytomegalovirus (CMV) is a virus that is endemic worldwide. A member of the herpes family, this virus discovered in 1957 is similar to EBV. The virus has been isolated from respiratory secretions, urine, semen, and cervical secretions, but it also found in transplanted organs and donor blood. Indeed,

Figure 10.12 Reactive lymphocytes. Note large cells with abundant basophilic cytoplasm.

Table 10.4 O Lymphocyte Morphologies

Figure 10.12 Reactive lymphocytes. Note large cells with abundant basophilic cytoplasm.

40% to 90% of all blood donors show anti-CMV titers, indicating that they have been exposed and have mounted an antibody response. Most individuals have a subclinical infection and do not even realize that they have had a viral infection. Some individuals have a mononucleosis-like syndrome with low-grade fever and flu-like symptoms. But to immunocompromised

Table 10.4 O Lymphocyte Morphologies

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