Acute Infectious Lymphocytosis Caused by Coxsackievirus B2

Abstract

Acute infectious lymphocytosis (AIL), a condition predominantly found in children, was first described by Smith in 1941.1 AIL is probably caused by several viruses.2-6 The incubation period lasts from 14 to 21 days. It is transferred by fecal-oral or airborne routes. The incidence and prevalence of the disease are unknown because infection is usually asymptomatic. The diagnosis is usually made by chance when a blood test is done. The cardinal sign of AIL is marked leukocytosis in the peripheral blood of the patient (40 to 100 × 109/liter) with prevalence of small, mature and morphologically normal lymphocytes. Often it is accompanied by eosinophilia. As a rule there is no anemia or thrombocytopenia.7 Similar changes are found in the patient's bone marrow.8 The patients do not look seriously ill. Their lymph nodes and spleens are rarely enlarged. The etiology of the disease is established by appropriate virologic tests. In the differential diagnosis AIL must be differentiated from whooping cough, infectious mononucleosis and leukemia. Lymphocytosis also occurs in other infectious diseases, autoimmune diseases, malignant diseases, granulomatous diseases, postimmunization states, drug reactions and graft rejection.9 The disease ends spontaneously and the laboratory tests return to normal within 4 to 10 weeks. Case report. HS, a 3-year-old boy of Gypsy origin, was evaluated at the Department of Infectious Diseases of the University Medical Centre in Ljubljana, Slovenia, because of fever, sore throat and abdominal pain. The boy was the third of four children in the family. The pregnancy, delivery and neonatal period were uneventful. The birth weight was 2600 g. Immunizations were performed according to the official immunization program in Slovenia. He had had diarrhea a few times but had never been seriously ill. The child fell ill on January 12, 1994 (5 days before admission to the hospital) with fever, abdominal pain, running nose and cough. On January 17 the blood tests revealed leukocytosis of 87.6 × 109/liter. At admission to the hospital, his axillary body temperature was 37.4°C and a serous discharge from the nose and sore throat were observed. The lymph nodes and spleen were not palpable. The abdomen was soft and painless. The liver edge was palpated 1 cm below the costal margin. During the 8-day hospitalization his symptoms and signs disappeared spontaneously and he was discharged from the hospital. Results of the laboratory tests are shown in Table 1. The consulted morphologist's opinion was normal lymphocytosis. Bone marrow evaluation was not done. The erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, alanine aminotransferase, serum proteins and chest radiograph were normal. Ultrasonography of the abdomen revealed an enlarged liver. A Mantoux test with purified protein derivative was nonreactive. Serologic studies for Epstein-Barr virus, cytomegalovirus, Bordetella pertussis, Toxoplasma gondii, Mycoplasma pneumoniae, Chlamydia psittaci and respiratory virus (influenza A, influenza B, adenovirus, respiratory syncytial virus, parainfluenza viruses 1, 2 and 3) were negative. A transnasal swab for B. pertussis culture was negative. Coxsackievirus B2 was isolated from the pharyngeal and stool swab specimens. The titers of neutralizing antibodies to coxsackievirus B2 were 1:4 on January 22 and 1:16 on February 4. On February 4 we examined the other children in the family (Table 2). Coxsackievirus B2 was isolated from pharyngeal and stool swab specimens of the three siblings. One sibling also showed lymphocytosis in peripheral blood with mild clinical symptoms and two other siblings demonstrated eosinophilia, suggesting that they were in the convalescence phase of AIL. Discussion. We describe a 3-year-old child with acute infectious lymphocytosis. According to the criteria of Lerner and Wilson10 the disease was caused by coxsackievirus B2. The etiology was proved by isolation of the virus from pharyngeal swab and stool specimens together with a significant rise of specifical neutralization antibodies in the patient's blood between the acute and convalescent sera. The same virus was also found in pharyngeal swabs and stools of the patient's siblings. All these findings favor the infectious nature of the disease and its spread in small outbreaks. The illness resolved without complications. Two years after the disease our patients remained healthy. Coxsackievirus B2 has been isolated in patients with carditis, pleurodynia, upper respiratory tract infection and neonatal infection. It probably also causes encephalitis, aseptic meningitis, paralytic disease, herpangina and exanthema. Our literature search (Medline 1966 to 1995) revealed no previous report of coxsackievirus B2 and acute infectious lymphocytosis. Maja Arnež, M.D.; Milan Cižman, M.D., Ph.D.; Janez Jazbec, M.D., M.Sci.; Antonija Kotnik, Dipl. Ing. Chem. Laboratory for Viruses and Rickettsiae; Institute of Public Health of the Republic of Slovenia (AK); University Department of Infectious Diseases; Department of Pediatrics (MA, MC); Division of Malignant Haematologic Disorders (JJ); University Medical Centre; Ljubljana, Slovenia