Congenital and Perinatal Cytomegalovirus Infection

The signs and symptoms of CMV infection vary with age, route of transmission, and immunocompetence of the patient.

Congenital Infection.
Symptomatic congenital CMV infection was originally termed cytomegalic inclusion disease. Only 5% of all congenitally infected infants have severe cytomegalic inclusion disease, another 5% have mild involvement, and 90% are born with subclinical, but still chronic, CMV infection. The characteristic signs and symptoms of clinically manifested infections include intrauterine growth restriction, prematurity, hepatosplenomegaly and jaundice, blueberry muffin–like rash, thrombocytopenia and purpura, and microcephaly and intracranial calcifications. Other neurologic problems include chorioretinitis, sensorineural hearing loss, and mild increases in cerebrospinal fluid protein. Symptomatic newborns are usually easy to identify. The most severe symptomatic congenital infections and those resulting in sequelae are more likely to be caused by primary rather than reactivated infections in pregnant women. Reinfection with a different strain of CMV can lead to symptomatic congenital infection. Asymptomatic congenital CMV infection is likely the leading cause of sensorineural hearing loss, which occurs in approximately 7% of all infants with congenital CMV infection, whether symptomatic at birth or not.

Perinatal Infection.
Infections resulting from exposure to CMV in the maternal genital tract at delivery or in breast milk occur despite the presence of maternally derived, passively acquired antibody.

Diagnosis of Poliomyelitis

Poliomyelitis should be considered in any unimmunized or incompletely immunized child with paralytic disease. VAPP should be considered in any child with paralytic disease occurring 7–14 days after receiving the orally administered polio vaccine (OPV). VAPP can occur at later times after administration, and should be considered in any child with paralytic disease in countries or regions where wild-type poliovirus has been eradicated and the OPV has been administered to the child or a contact. The combination of fever, headache, neck and back pain, asymmetric flaccid paralysis without sensory loss, and pleocytosis does not regularly occur in any other illness.

Identification of Poliovirus in Stool:
The World Health Organization (WHO) recommends that the laboratory diagnosis of poliomyelitis be confirmed by isolation and identification of poliovirus in the stool, with specific identification of wild-type and vaccine-type strains. In suspected cases of acute flaccid paralysis, 2 stool specimens should be collected 24–48 hr apart, as soon as possible after the diagnosis of poliomyelitis is suspected. Poliovirus concentrations are high in the stool in the 1st week after the onset of paralysis, which is the optimal time for collection of stool specimens. Polioviruses may be isolated from 80–90% of acutely ill patients, whereas <20% may yield virus within 3–4 wk after onset of paralysis. Because most children with spinal or bulbospinal poliomyelitis have constipation, rectal straws may be used to obtain specimens; ideally a minimum of 8–10 g of stool should be collected. In laboratories that can isolate poliovirus, isolates should be sent to either the Centers for Disease Control and Prevention or to 1 of the WHO-certified poliomyelitis laboratories where DNA sequence analysis can be performed to distinguish between wild poliovirus and neurovirulent, revertant OPV strains. With the current WHO plan for global eradication of poliomyelitis, most regions of the world (the Americas, Europe, Australia) have been certified wild-poliovirus free; in these areas, poliomyelitis is most often caused by vaccine strains. Hence it is critical to differentiate between wild-type and revertant vaccine-type strains.

Clinical Manifestations in Infants of Diabetic Mothers

Infants of diabetic and gestational diabetic mothers often bear a surprising resemblance to each other. They tend to be large and plump as a result of increased body fat and enlarged viscera, with puffy, plethoric facies resembling that of patients who have been receiving corticosteroids. These infants may also, however, be of normal or low birthweight, particularly if delivered before term or the mother has associated vascular disease.

Hypoglycemia develops in about 25–50% of infants of diabetic mothers and 15–25% of infants of mothers with gestational diabetes, but only a small percentage of these infants become symptomatic. The probability of hypoglycemia developing in the infant increases and glucose levels are likely to be lower at higher cord or maternal fasting blood glucose levels. The nadir in an infant’s blood glucose concentration is usually reached between 1 and 3 hr; spontaneous recovery may begin by 4–6 hr.

The infants tend to be jumpy, tremulous, and hyperexcitable during the 1st 3 days of life, although hypotonia, lethargy, and poor sucking may also occur. They may have any of the diverse manifestations of hypoglycemia. Early appearance of these signs is more likely to be related to hypoglycemia and later appearance related to hypocalcemia; these abnormalities may also occur together. Perinatal asphyxia or hyperbilirubinemia may produce similar signs. Hypomagnesemia may be associated with the hypocalcemia. These manifestations may also occur in the absence of hypoglycemia, hypocalcemia, or asphyxia.

Laboratory Findings in Juvenile Rheumatoid Arthritis

Hematologic abnormalities often reflect the degree of systemic or articular inflammation, with elevated white blood cell and platelet counts and decreased hemoglobin concentration and mean corpuscular volume. The ESR and CRP usually mirror these findings, along with elevated serum immunoglobulins. It is not unusual for the ESR to be normal in some children with chronic arthritis. Because platelets are an acute-phase reactant, a high ESR and neutropenia with a low platelet count may be a clue to leukemia as a cause of periarticular swelling and pain.

Elevated ANA titers are present in at least 40–85% of children with oligoarticular or polyarticular JRA, but are unusual in children with systemic-onset disease. ANA seropositivity is associated with increased risk for the development of chronic uveitis in a child with limited joint disease.

Rheumatoid-factor (RF) seropositivity may be associated with onset of polyarticular involvement in an older child (?8%) and the development of rheumatoid nodules, and with a poor overall prognosis with eventual functional disability. Both ANA and RF seropositivity occur in association with transient events during childhood, such as viral infections, particularly Epstein-Barr virus. Seropositivity for both ANA and RF must be defined at a specific titer in relation to accepted positive and negative controls and a laboratory-defined coefficient of variation.

Brief Summary of Clinical Features of Diabetes in Children

As diabetes develops, symptoms steadily increase, reflecting the decreasing -cell mass, worsening insulinopenia, progressive hyperglycemia, and eventual ketoacidosis. Initially, when only insulin reserve is limited, occasional hyperglycemia occurs. When the serum glucose increases above the renal threshold, intermittent polyuria or nocturia begins. With further ?-cell loss, chronic hyperglycemia causes a more persistent diuresis, often with nocturnal enuresis, and polydipsiabecomes more apparent. Female patients may develop monilial vaginitis due to the chronic glycosuria. Calories are lost in the urine (glycosuria), triggering a compensatory hyperphagia. If this hyperphagia does not keep pace with the glycosuria, loss of body fat ensues, with clinical weight loss and diminished subcutaneous fat stores.

An average, healthy 10-yr-old child consumes about 50% of 2,000 daily calories as carbohydrate. As that child becomes diabetic, daily losses of water and glucose may be 5 L and 250 g, respectively, representing 1,000 calories, or 50%, of the average daily caloric intake. Despite the child’s compensatory increased intake of food, the body starves because unused calories are lost in the urine.

When extremely low insulin levels are reached, keto acids accumulate. At this point, the child quickly deteriorates. Keto acids produce abdominal discomfort, nausea, and emesis, preventing oral replacement of urinary water losses. Dehydration accelerates, causing weakness or orthostasis—but polyuria persists. As in any hyperosmotic state, the degree of dehydration may be clinically underestimated because intravascular volume is conserved at the expense of intracellular volume. Ketoacidosis exacerbates prior symptoms and leads to Kussmaul respirations (deep, heavy, rapid breathing), fruity breath odor (acetone), diminished neurocognitive function, and possible coma. About 20–40% of children with new-onset diabetes progress to DKA before diagnosis.

Complications of Varicella Zoster Virus Infection in Children

The complications of VZV infection occur with varicella, or with reactivation of infection, more commonly in immunocompromised patients. In the otherwise healthy child, mild varicella hepatitis is relatively common but rarely clinically symptomatic.

Mild thrombocytopenia occurs in 1–2% of children with varicella and may be associated with transient petechiae. Purpura, hemorrhagic vesicles, hematuria, and gastrointestinal bleeding are rare complications that may have serious consequences.

Cerebellar ataxia occurs in 1 in every 4,000 cases. Other complications of varicella, some of them rare, include encephalitis, pneumonia, nephritis, nephrotic syndrome, hemolytic-uremic syndrome, arthritis, myocarditis, pericarditis, pancreatitis, and orchitis.

Secondary Bacterial Infections.
Secondary bacterial infections of the skin, usually caused by group A streptococci and S. aureus, may occur in up to 5% of children with varicella. These range from superficial impetigo to cellulitis, lymphadenitis, and subcutaneous abscesses. An early manifestation of secondary bacterial infection is erythema of the base of a new vesicle. Recrudescence of fever 3–4 days after the initial exanthem may also herald a secondary bacterial infection. Varicella is a well-described risk factor for serious invasive infections caused by group A streptococcus, which can have a fatal outcome. The more invasive infections, such as varicella gangrenosa, bacterial sepsis, pneumonia, arthritis, osteomyelitis, cellulitis, and necrotizing fasciitis, account for much of the morbidity and mortality of varicella in otherwise healthy children. Bacterial toxin-mediated diseases (toxic shock syndrome) also may complicate varicella. A substantial decline in varicella-related invasive bacterial infections has been associated with the use of the varicella vaccine.