Dr Ira Shah
M.D, DNB, DCH(Gold Medalist), FCPS

A seven years old female child presented with swellings over both axillae and in the neck since 1 month. On examination, she had bilateral mobile axillary lymphnodes - (largest 3cm x 3cm) with multiple small mobile, non-tender cervical and inguinal lymph nodes. She also had a firm hepatosplenomegaly. Her anthropometry was in the 50th percentiles ruling out chronic malnutrition. She had received anti-tuberculous therapy 6 years back for 8 months in view of primary complex. With the above clinical picture a differential diagnosis of infectious mononucleosis, reactive lymphadenopathy, Koch's, HIV and malignancy were considered. Her hemoglobin was 7.4 gm% with WBC count of 12,600/cu mm with 61% polymorphs, 38% lymphocytes and 1% monocytes. ESR was 5 mm after 1 hour. Her ELISA for HIV was negative and X-ray chest was normal. Her GL for AFB was negative. Peripheral smear did not show any abnormal cells. An ultrasound of the abdomen was suggestive of lymphomatous deposits of 5 mm in inferior pole of spleen with splenomegaly. Axillary lymphnode biopsy was done which showed loss of architecture with prominent lymphoid follicles, expanded centres and active phagocytosis with mild blurring of follicles and reactive sinusoidal change suggestive of a florid antigenic stimulation like a recent viral or toxoplasma infection. Her serology by EIA for toxoplasma, rubella and cytomegalovirus was done which showed both increased CMV IgM [2.95 IU/ml (Normal = 0.0 - 0.25 IU/ml)] and increased CMV IgG [1.88 IU/ml (Normal = 0.0 - 1.0 IU/ml)]. Her titres for Rubella IgG & IgM and Toxoplasma IgM & IgG were negative. Thus, a diagnosis of infectious mononucleosis due to CMV infection was confirmed. She was advised follow up after a period of 1 month.

CMV is a member of the Herpes viridae family of DNA viruses. Infection with CMV is common and usually unapparent.

Transmission: CMV transmission is highest in:

Early childhood


Adolescence


Child bearing years

1% of all newborns are born congenitally infected with CMV. Acquired CMV usually occurs in 80% of children by 3 years of age in patients from low socio-economic strata in developing countries. Children excrete CMV in their saliva and urine and lead to a high prevalence of horizontal spread. In adolescents, it is attributed to intimate physical contact. Nosocomial transmission occurs with blood product transfusion, BMT & organ transplantation.

Pathogenesis: CMV infection can involve virtually any organ of the body leading to intranuclear inclusions and massive enlargement of the affected cells.

Infection with CMV can be latent and non-productive, productive yet asymptomatic, or productive and symptomatic. T cell immunity especially cytotoxic T cells generation is the most important parameter for effective immune response.

Mononucleosis syndrome: Fever and severe malaise of about 1 to 4 weeks duration, lymphocytosis with atypical lymphocytes and mild elevation of liver enzymes are the common manifestations.

It rarely causes pharyngitis, tonsillitis or significant splenomegaly as in Epstein-Barr induced mononucleosis. It can cause a morbilliform rash after ampicillin administration. Complications include - interstitial pneumonitis, myocarditis, pericarditis, hemolytic anemia, thrombocytopenia, hemophagocytic syndrome, adrenal insufficiency, GBS, meningoencephalitis and severe icteric hepatitis. CMV retinitis is seen in patients on immunosuppression or patients with AIDS.

Mononucleosis seen by other viruses such as EBV, Hep A, Hep B and HIV as well as acquired toxoplasmosis.

Diagnosis:

Isolation of virus - Skin, urine, saliva, conjunctive stool, cervicovaginal secretions.


CMV - DNA PCR


Serology - Seroconversion or a fourfold rise in CMV-IgG. Positive IgM-CMV by RIA, IFA or ELISA. (IFA is most reliable). In healthy adults, CMV IgM antibody usually persists for 6 weeks and may be present up to 3 to 6 months after primary infection occurs.

In an a typical case presenting with lymphadenopathy without fever, sorethroat or splenomegaly, a lymphnode biopsy may be required to rule out malignant lymphoma. Microscopically there is predominant sinusal distribution of the large lymphoid cells, follicular hyperplasia with marked mitotic activity increase in plasma cells and vascular proliferation. Though the nodal architecture appears effected, the sinusoidal pattern remains intact.

Ganciclovir - For life-threatening infections with CMV. It is virostatic and so suppresses active CMV infection but does not produce a cure. It is indicated for treatment of CMV retinitis, pneumatosis.

Induction - 5 mg/kg/dose IV bd for 2-3 weeks.

Following induction - Maintenance of 5 mg/kg/day for 5-7 days of the week.