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.

Introduction to Esophageal Varices in Children

Portal hypertension is defined as an elevation of portal venous pressure to levels 10–12 mm Hg higher than pressures present in the inferior vena cava. Decompression of this hypertension through portosystemic collateral circulation via the coronary vein, in conjunction with the left gastric veins, gives rise to esophageal varices. Most esophageal varices are “uphill varices”; less commonly, those that arise in the absence of portal hypertension and with superior vena cava (SVC) obstruction are termed “downhill varices.” Their treatment is directed at the underlying cause of the SVC abnormality.

Clinical Presentation:
Hemorrhage from esophageal varices is the major cause of morbidity and mortality due to portal hypertension. Presentation is with significant hematemesis and melena; whereas most patients have liver disease, some children with entities such as extrahepatic portal venous thrombosis may have been previously asymptomatic. Any child with hematemesis and splenomegaly should be presumed to have esophageal variceal bleeding until proven otherwise.

Diagnosis:
Varices are occasionally seen on fluoroscopic barium contrast studies, but upper endoscopy is preferred because it provides definitive diagnosis as well as therapy for acute bleeding episodes via either sclerotherapy or band ligation.

Laboratory Findings in Hypoparathyroidism

The serum calcium level is low (5–7 mg/dL), and the phosphorus level is elevated (7–12 mg/dL).

Blood levels of ionized calcium (usually approximately 45% of the total) more nearly reflect physiologic adequacy but also are low.

The serum level of alkaline phosphatase is normal or low, and the level of 1,25[OH]2D3 is usually low, but high levels have been found in some children with severe hypocalcemia.

The level of magnesium is normal but should always be checked in hypocalcemic patients.

Levels of PTH are low when measured by immunometric assay.

Administration of the synthetic 1–34 fragment of human PTH (teriparatide acetate) results in increased urinary levels of cyclic adenosine monophosphate and phosphate. This response differentiates hypoparathyroidism from pseudohypoparathyroidism. With the advent of very sensitive PTH assays, this test is usually not necessary.

Cardiac Examination in Children

The heart should be examined in a systematic manner starting with inspection and palpation.

A precordial bulge to the left of the sternum with increased precordial activity suggests cardiac enlargement; such bulges can often best be appreciated by having the child lay supine with the examiner looking up from the child’s feet.

A substernal thrust indicates the presence of right ventricular enlargement, whereas an apical heave is noted with left ventricular hypertrophy.

A hyperdynamic precordium suggests a volume load such as that found with a large left-to-right shunt, although it may be normal in a thin patient.

A silent precordium with a barely detectable apical impulse suggests pericardial effusion or severe cardiomyopathy; it may be normal in an obese patient.

The relationship of the apical impulse to the midclavicular line is also helpful in the estimation of cardiac size: the apical impulse moves laterally and inferiorly with enlargement of the left ventricle. Right-sided apical impulses signify dextrocardia, tension pneumothorax, or left-sided thoracic space-occupying lesions (e.g., diaphragmatic hernia).

Thrills are the palpable equivalent of murmurs and correlate with the area of maximal auscultatory intensity of the murmur. It is important to palpate the suprasternal notch and neck for aortic bruits, which may indicate the presence of aortic stenosis or, when faint, pulmonary stenosis. Right lower sternal border and apical systolic thrills are characteristic of ventricular septal defect and mitral insufficiency, respectively. Diastolic thrills are occasionally palpable in the presence of atrioventricular valve stenosis. The timing and localization of thrills should be carefully noted.

Auscultation is an art that improves with practice. The diaphragm of the stethoscope is placed firmly on the chest for high-pitched sounds; a lightly placed bell is optimal for low-pitched sounds. The physician should initially concentrate on the characteristics of the individual heart sounds and their variation with respirations and later concentrate on murmurs. The patient should be supine, lying quietly, and breathing normally. The 1st heart sound is best heard at the apex, whereas the 2nd heart sound should be evaluated at the upper left and right sternal borders. The 1st heart sound is caused by closure of the atrioventricular valves (mitral and tricuspid); the 2nd sound is caused by closure of the semilunar valves (aortic and pulmonary) .During inspiration, the decrease in intrathoracic pressure results in increased filling of the right side of the heart, which leads to an increased right ventricular ejection time and thus delayed closure of the pulmonary valve; consequently, splitting of the 2nd heart sound increases during inspiration and decreases during expiration.

Clinical Features of Scarlet Fever

Scarlet fever is an upper respiratory tract infection associated with a characteristic rash, which is caused by an infection with pyrogenic exotoxin (erythrogenic toxin)–producing Group A Streptococcus in individuals who do not have antitoxin antibodies. It is now encountered less commonly and is less virulent than in the past, but the incidence is cyclic, depending on the prevalence of toxin-producing strains and the immune status of the population. The modes of transmission, age distribution, and other epidemiologic features are otherwise similar to those for GAS pharyngitis.

Rash:
The rash appears within 24–48 hr after onset of symptoms, although it may appear with the 1st signs of illness . It often begins around the neck and spreads over the trunk and extremities. It is a diffuse, finely papular, erythematous eruption producing a bright red discoloration of the skin, which blanches on pressure. It is often more intense along the creases of the elbows, axillae, and groin. The skin has a goose-pimple appearance and feels rough. The face is usually spared, although the cheeks may be erythematous with pallor around the mouth. After 3–4 days, the rash begins to fade and is followed by desquamation, 1st on the face, progressing downward, and often resembling that seen subsequent to a mild sunburn. Occasionally, sheetlike desquamation may occur around the free margins of the fingernails, the palms, and the soles.

Pharynx:
Examination of the pharynx of a patient with scarlet fever reveals essentially the same findings as with GAS pharyngitis.

Hemorrhagic Disease of Newborn

A moderate decrease in factors II, VII, IX, and X normally occurs in all newborn infants by 48–72 hr after birth, with a gradual return to birth levels by 7–10 days of age. This transient deficiency of vitamin K–dependent factors is probably due to lack of free vitamin K from the mother and absence of the bacterial intestinal flora normally responsible for the synthesis of vitamin K. Rarely, in term infants and more frequently in premature infants, accentuation and prolongation of this deficiency between the 2nd and 7th days of life result in spontaneous and prolonged bleeding. Breast milk is a poor source of vitamin K, and hemorrhagic complications are more frequent in breast-fed than in formula-fed infants. This classic form of hemorrhagic disease of the newborn, which is responsive to and prevented by vitamin K therapy, must be distinguished from disseminated intravascular coagulopathy and from the more infrequent congenital deficiencies of one or more of the other factors that are unresponsive to vitamin K.

Early-onset life-threatening vitamin K deficiency–induced bleeding(onset from birth to 24 hr) also occurs if the mother has been treated with drugs (phenobarbital, phenytoin) that interfere with vitamin K function.

Late onset (>2 wk) is often associated with vitamin K malabsorption, as noted in neonatal hepatitis or biliary atresia.

Clinical Features:
Hemorrhagic disease of the newborn resulting from severe transient deficiencies in vitamin K–dependent factors is characterized by bleeding that tends to be gastrointestinal, nasal, subgaleal, intracranial, or postcircumcision. Prodromal or warning signs (mild bleeding) may occur before serious intracranial hemorrhage.

Introduction to Hemophilia

A hereditary bleeding disorder, hemophilia results from the deficiency of specific clotting factors. Hemophilia A (classic hemophilia), which affects more than 80% of all hemophiliacs, results from a deficiency of factor VIII; hemophilia B (Christmas disease), which affects 15% of hemophiliacs, results from a deficiency of factor IX.
The severity and prognosis of bleeding disorders vary with the degree of deficiency and the site of bleeding. The overall prognosis is best in mild hemophilia, which doesn’t cause spontaneous bleeding and joint deformities.
Advances in treatment have greatly improved the prognosis, and many hemophiliacs live normal life spans. Surgical procedures can be done safely at special treatment centers for hemophiliacs under the guidance of a hematologist.

Causes
Hemophilia is caused by a deficiency of clotting factors that are genetically transmitted.

Incidence
Hemophilia is the most common X-linked genetic disease, occurring in about 1.25 in 10,000 live male births. Hemophilia A is five times more common than hemophilia B. Hemophilia causes abnormal bleeding because of a specific clotting factor malfunction. After a person with hemophilia forms a platelet plug at a bleeding site, clotting factor deficiency impairs the capacity to form a stable fibrin clot.

Signs and symptoms
Hemophilia produces abnormal bleeding, which may be mild, moderate, or severe, depending on the degree of factor deficiency.

Treatment of Pancreatic Insufficiency

Treatment of exocrine pancreatic insufficiency by oral enzyme replacement usually corrects steatorrhea, but steatorrhea is difficult to correct completely. This is due to variability of lipase activity in different commercial preparations, inadequate dosage, incorrect timing of doses, lipase inactivation by gastric acid, and the observation that chymotrypsin in the enzyme preparation digests and thus inactivates lipase. In enzyme supplements, the true lipase activity has been shown to be as much as twice the labeled amount. Pancrease, Creon, Ultrase, and Panceacarb are the preparations most widely used. These products are enteric-coated preparations that resist gastric acid inactivation. Generic enzyme preparations are less effective and should be avoided.

The dosage of pancreatic replacement for children depends on the amount of food eaten and is established by trial and error. Because these products contain excess protease compared with lipase, the dosage is estimated from the lipase requirement of 500–1,500 IU/kg/meal. An adequate dose is one that is followed by the return of the stools to normal fat content, size, color, and odor. Enzyme replacement should be given at the beginning of and with the meal. Tablets should be chewed; powder and granules can be mixed with a small quantity of food. Enzymes must also be given with snacks. Increasing enzyme supplements beyond the recommended dose does not improve absorption, may retard growth, and may cause fibrosing colonopathy.

History in Cardiovascular Evaluation Of Children

The importance of the history and physical examination cannot be overemphasized in the evaluation of infants and children with suspected cardiovascular disorders. Patients may require further laboratory evaluation and eventual treatment, or the family may be reassured that no significant problem exists.

A comprehensive cardiac history starts with details of the perinatal period including the presence of cyanosis, respiratory distress, or prematurity.

Maternal complications such as gestational diabetes, medications, systemic lupus erythematosus, or substance abuse can be associated with cardiac problems.

If cardiac symptoms began during infancy, the timing of the initial symptoms should be noted to provide important clues about the specific cardiac condition.

Many of the symptoms of heart failure in infants and children are age specific. In infants, feeding difficulties are common. Inquiry should be made about the frequency of feeding and either the volume of each feeding or the time spent on each breast. An infant with heart failure often takes less volume per feeding and becomes dyspneic or diaphoretic while sucking. After falling asleep exhausted, the baby, inadequately fed, will awaken for the next feeding after a brief time. This cycle continues around the clock and must be carefully differentiated from colic or other feeding disorders. Additional symptoms and signs include those of respiratory distress: rapid breathing, nasal flaring, cyanosis, and chest retractions. In older children, heart failure may be manifested as exercise intolerance, difficulty keeping up with peers during sports or need for a nap after coming home from school, and poor growth. Eliciting a history of fatigue in an older child requires questions about age-specific activities, including stair climbing, walking, bicycle riding, physical education class, and competitive sports; information should be obtained regarding more severe manifestations such as orthopnea and nocturnal dyspnea.

Congenital Complete Atrio-ventricular Block

Congenital complete AV block in children is most often caused by autoimmune injury of the fetal conduction system by maternally derived IgG antibodies (anti-SSA/Ro, anti-SSB/La) in a mother with overt or, more often, asymptomatic SLE or Sjögren syndrome. Autoimmune disease accounts for 60–70% of all cases of congenital complete heart block and ?80% of cases in which the heart is structurally normal.

Complete heart block is also seen in patients with complex congenital heart disease and abnormal embryonic development of the conduction system. It has been associated with myocardial tumors and myocarditis. It is a known complication of myocardial abscess secondary to endocarditis. It is also seen in genetic abnormalities including LQTS and Kearn-Sayre syndrome. It is also a complication of congenital heart disease repair.

Incidence:
The incidence of congenital complete heart block is 1/20,000-25,000 live births; a high fetal loss rate may cause an underestimation of its true incidence. In some infants of mothers with SLE, complete heart block is not present at birth but develops within the 1st 3–6 mo after birth.

Clinical Manifestations:
The arrhythmia is often diagnosed in the fetus (secondary to the dissociation between atrial and ventricular contractions seen on fetal echocardiography) and may produce hydrops fetalis. Infants with associated congenital heart disease and heart failure have a high mortality rate.

Clinical Manifestations Of Poliomyelitis

Poliovirus infections with wild-type virus may follow 1 of several courses: inapparent infection, which occurs in 90–95% of cases and causes no disease and no sequelae; abortive poliomyelitis; nonparalytic poliomyelitis; or paralytic poliomyelitis. Paralysis, if it occurs, appears 3–8 days after the initial symptoms.

Incubation Period:
The incubation period of poliovirus from contact to initial clinical symptoms is usually considered to be 8–12 days, with a range of 5–35 days.

Abortive Poliomyelitis.In about 5% of patients, a nonspecific influenza-like syndrome occurs 1–2 wk after infection, which is termed abortive poliomyelitis. Fever, malaise, anorexia, and headache are prominent features, and there may be sore throat and abdominal or muscular pain. Vomiting occurs irregularly. The illness is short lived, up to 2–3 days. The physical examination may be normal or may reveal nonspecific pharyngitis, abdominal or muscular tenderness, and weakness. Recovery is complete, and no neurologic signs or sequelae develop.

Nonparalytic Poliomyelitis.
In about 1% of patients infected with wild-type poliovirus, signs of abortive poliomyelitis are present, as are more intense headache, nausea, and vomiting, as well as soreness and stiffness of the posterior muscles of the neck, trunk, and limbs. Fleeting paralysis of the bladder and constipation are frequent. Some of these children have a short symptom-free interlude between the 1st phase (minor illness) and the 2nd phase (CNS disease or major illness). Nuchal and spinal rigidity are the basis for the diagnosis of nonparalytic poliomyelitis during the 2nd phase.

Physical examination reveals nuchal-spinal signs and changes in superficial and deep reflexes. Gentle forward flexion of the occiput and neck will elicit nuchal rigidity. Head drop is demonstrated by placing the hands under the patient’s shoulders and raising the trunk. Although normally the head follows the plane of the trunk, in poliomyelitis it often falls backward limply, but this is not due to true paresis of the neck flexors. In struggling infants it may be difficult to distinguish voluntary resistance from clinically important true nuchal rigidity. One may place the infant’s shoulders flush with the edge of the table, support the weight of the occiput in the hand, and then flex the head anteriorly. True nuchal rigidity will persist during this maneuver. When open, the anterior fontanel may be tense or bulging.

Diagnosing Inflammatory Bowel Disease In Children

The laboratory evaluation of a patient with possible IBD is crucial to making the diagnosis, yet there is not one specific laboratory result that is pathognomonic of IBD.

Acute-phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are sensitive markers of acute inflammation, but are nonspecific, and may also be less accurate in patients with chronic nutritional deficiencies, including hypoproteinemia.

Liver assessment is important but also nonspecific. It can uncover mild abnormalities in the transaminase levels in CD, or help identify the 10% to 15% of patient with UC who also have sclerosing cholangitis, an autoimmune disease of the biliary tract that may be even more devastating to the patient than UC itself.

A complete blood count and peripheral smear often uncover the microcytic anemia of iron deficiency, resulting from either chronic GI blood loss, poor intake of iron in the diet, or malabsorption of enteral iron. Macrocytic anemia can be seen in IBD patients with a history of terminal ileal resection or chronic disease, due to poor absorption of vitamin B12, or rarely in patients with proximal small bowel disease who malabsorb folic acid.

Lipase may be useful to check, because a small percentage of CD patients may manifest pancreatitis due to CD, or possibly due to medications commonly used for the treatment of IBD.

Brief Summary of Coarctation of Aorta

Critical neonatal coarctation of the aorta is associated with ductal-dependent systemic blood flow provided by the RV.

Age of Presentation: Most often these infants present to a hospital at 2 to 6 weeks of life with a history of feeding and respiratory difficulties as the ductus arteriosus closes.

Clinical Features: The clinical exam suggests neonatal sepsis with gray mottled skin color and poor perfusion, tachypnea, and poor pulses. A murmur may not be apparent and hepatomegaly and gallop rhythm may be more detectable after fluid resuscitation. Oximetry may not reveal significant desaturation. Cardiomegaly is usually present on a chest radiograph.
Older children with coarctation usually have no symptoms but may have hypertension incidentally detected (especially if measured in the right arm). Femoral pulses can be present in the older child with coarctation due to flow through collateral vessels, and foot pulses may seem almost normal. However, palpation of femoral arterial pulse simultaneously with right brachial pulses will reveal the delay in femoral pulse and the relative decrease in amplitude.
A small number of infants will have noncritical but severe coarctation and present in the first 6 months of life with symptoms of congestive heart failure but without the picture of shock seen in the young infant with critical coarctation.

Management
Most infants with critical pulmonic valve stenosis will undergo urgent balloon dilation of the pulmonic valve in the catheterization lab. The infant with critical coarctation or critical aortic stenosis in cardiogenic shock requires stabilization by establishing patency of the ductus arteriosus to allow the RV to provide systemic blood flow below the aortic obstruction.

Clinical Manifestations of Hemolytic Disease of Newborn Caused by Rh Incompatibility

The Rh antigenic determinants are genetically transmitted from each parent, determine the Rh type, and direct the production of a number of blood group factors (C, c, D, d, E, and e). Each factor can elicit a specific antibody response under suitable conditions; 90% are due to D antigen and the remainder to C or E.

A wide spectrum of hemolytic disease occurs in affected infants born to sensitized mothers, depending on the nature of the individual immune response.

The severity of the disease may range from only laboratory evidence of mild hemolysis (15% of cases) to severe anemia with compensatory hyperplasia of erythropoietic tissue leading to massive enlargement of the liver and spleen. When the compensatory capacity of the hematopoietic system is exceeded, profound anemia occurs and results in pallor, signs of cardiac decompensation (cardiomegaly, respiratory distress), massive anasarca, and circulatory collapse. This clinical picture of excessive abnormal fluid in two or more fetal compartments (skin, pleura, pericardium, placenta, peritoneum, amniotic fluid), termed hydrops fetalis, frequently results in death in utero or shortly after birth. With the use of RhoGAM to prevent Rh sensitization, nonimmune (nonhemolytic) conditions have become frequent causes of hydrops . The severity of hydrops is related to the level of anemia and the degree of reduction in serum albumin (oncotic pressure), which is due in part to hepatic dysfunction. Alternatively, heart failure may increase right heart pressure, with the subsequent development of edema and ascites. Failure to initiate spontaneous effective ventilation because of pulmonary edema or bilateral pleural effusions results in birth asphyxia; after successful resuscitation, severe respiratory distress may develop. Petechiae, purpura, and thrombocytopenia may also be present in severe cases as a result of decreased platelet production or the presence of concurrent disseminated intravascular coagulation.

Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome (SDS) is inherited in an autosomal recessive manner; it occurs in all racial and ethnic groups. Essential diagnostic criteria are exocrine pancreatic insufficiency and variable hematologic cytopenias due to marrow failure.

Pathology
The mutant gene SBDS maps to chromosome 7q11 and is responsible for the multisystem, pleiotropic phenotype in 90% of cases. Pancreatic insufficiency is due to failure of pancreatic acinar development. Fatty replacement of pancreatic tissue is prominent. Bone marrow failure is characterized by a generalized marrow cell and microenvironmental dysfunction that does not support and maintain normal hematopoiesis.

Clinical Manifestations.
Although most patients have symptoms of fat malabsorption from birth caused by pancreatic insufficiency, the absence of steatorrhea does not exclude a diagnosis of SDS. Approximately 50% of patients appear to exhibit a modest improvement in pancreatic enzyme secretion with advancing age.

Short stature is a consistent feature of the syndrome; most patients show normal growth velocity, yet remain consistently below the 3rd percentile for height and weight. The occasional adult achieves the 25th percentile for height.

Treatment of Kawasaki Disease

Patients with acute Kawasaki disease should be treated with intravenous immunoglobulin (IVIG) and high-dose aspirin as soon as possible after diagnosis and, ideally, within 10 days of disease onset.

The mechanism of action of IVIG in Kawasaki disease is unknown, but treatment should result in rapid defervescence and resolution of clinical signs of illness in 85–90% of patients. With therapy, the CRP normalizes much more quickly than the ESR, which will often increase immediately after IVIG therapy. IVIG reduces the prevalence of coronary disease from 20–25% in children treated with aspirin alone to 2–4% in those treated with IVIG and aspirin within the 1st 10 days of illness. Consideration should even be given to treatment of patients diagnosed after the 10th illness day if fever has persisted, because the anti-inflammatory effect may be helpful, although the effect of such therapy on the risk of developing coronary aneurysms is unknown. The dose of aspirin is decreased from anti-inflammatory to antithrombotic doses (3–5 mg/kg/day as a single dose) on the 14th illness day or after the patient has been afebrile for at least 3–4 days. Aspirin is continued for its antithrombotic effect until 6–8 wk after onset, when the ESR has normalized in patients that have not developed abnormalities detected by echocardiography.

Brief Summary of Tumor Lysis Syndrome

Tumor lysis syndrome consists of hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia in a patient presenting with leukemia or lymphoma, especially those with a very high white blood cell count, Burkitt leukemia/lymphoma, or T-cell leukemia/lymphoma.

Cause:
Tumor lysis can occur prior to the onset of therapy due to spontaneous blast cell breakdown, but more typically occurs after initiating therapy. Tumor lysis syndrome has rarely been reported in children with other solid tumors. In order to prevent acute renal failure, it is essential that tumor lysis be treated aggressively.

Laboratory tests:
A patient with suspected tumor lysis syndrome should have the following laboratory studies performed at the time of presentation: CBC with manual differential, and chemistry panel (to include potassium, creatinine, calcium, phosphorus, and uric acid).

Therapy:

• Therapy for tumor lysis syndrome includes IV hydration at 2 or more times maintenance (~3,000 mL/m2/day), urinary alkalinization, and allopurinol to decrease the formation of uric acid.
• Potassium should not be included in the IV fluid.

Clinical Manifestations of Classic Phenylketonuria (PKU).

Severe hyperphenylalaninemia (plasma phenylalanine levels >20 mg/dL), if untreated, invariably results in the development of signs and symptoms of classic PKU, except in rare unpredictable occasions.

Clinical Features:
The affected infant is normal at birth. Mental retardation may develop gradually and may not be evident for the 1st few months. It is usually severe, and most patients require institutional care if the condition remains untreated. Vomiting, sometimes severe enough to be misdiagnosed as pyloric stenosis, may be an early symptom. Older untreated children become hyperactive, with purposeless movements, rhythmic rocking, and athetosis.

Physical Examination:
On physical examination, these infants are lighter in their complexion than unaffected siblings. Some may have a seborrheic or eczematoid rash, which is usually mild and disappears as the child grows older. These children have an unpleasant odor of phenylacetic acid, which has been described as musty or mousey. There are no consistent findings on neurologic examination. Most infants are hypertonic with hyperactive deep tendon reflexes. About 25% of children have seizures, and more than 50% have electroencephalographic abnormalities. Microcephaly, prominent maxilla with widely spaced teeth, enamel hypoplasia, and growth retardation are other common findings in untreated children.

Introduction to Hemolytic-Uremic Syndrome.

Hemolytic-uremic syndrome (HUS), first described in 1955, is a heterogeneous syndrome characterized by a triad of microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. Initially thought to be a sporadic process, it is now recognized as the most common cause of acute renal failure in children.

Pathogenesis:
In D+ HUS (post diarrheal hemolytic uremic syndrome), with Shiga toxin-producing E. coli O157:H7 infection, the toxin binds, invades, and causes destruction of colonic epithelial cells, resulting in bloody diarrhea. Presumably because of the inflamed colon allowing transmural absorption, the toxin then enters the blood circulation. There the toxin binds to a glycolipid receptor known as globotriaosylceramide (Gb3), which results in endocytosis of the toxin usually within renal glomerular endothelial cells, and at times, other target organs. The expression of Gb3 receptors appears to be higher in infants and young children, which may in part explain the age-related propensity for developing HUS. Older children and adults have lower numbers of these receptors but may develop HUS whenever the combined effect of lipopolysaccharide and cytokines upregulate the expression of these Gb3 receptors.

Clinical Features:
With STEC (Shiga toxin producing E coli) infection, the incubation period is typically 3 to 4 days after exposure (range, 1 to 14 days).

Introduction to Sjögren Syndrome in Children

Sjögren syndrome is a chronic, inflammatory, autoimmune disease characterized by progressive lymphocytic and plasma cell infiltration of the salivary and lacrimal glands.

Epidemiology.
Sjögren syndrome typically presents at 35–45 yr of age, with 90% of cases among women. It is uncommon in the pediatric age group. Sjögren syndrome can occur as an isolated disorder, referred to as primary Sjögren syndrome (sicca complex), or as a secondary form in association with other rheumatic disorders.

Etiology And Pathogenesis.
The etiology of Sjögren syndrome is complex and includes genetic predisposition, and possibly an infectious trigger. Lymphocytes and plasma cells infiltrate salivary glands, forming distinct periductal and periacinar foci that become confluent and may replace epithelial structure. This autoimmune exocrinopathy results in xerophthalmia (dry eyes, or keratoconjunctivitis sicca) and xerostomia (dry mouth). Several genes regulating apoptosis influence the chronicity of lymphocytic infiltration.

Clinical Manifestations.
International classification criteria for the diagnosis of Sjögren syndrome in adult patients have been developed, and diagnostic criteria in children have been proposed. Clinical manifestations are related to exocrine disease of the epithelial surfaces of the eyes, mouth, nose, larynx and trachea, vagina, and skin, leading to the common symptoms of photophobia, burning and itching eyes, blurred vision, painless unilateral or bilateral enlargement of the parotid glands, decreased sense of taste, dental caries, dysphagia, fissured tongue, and angular cheilitis. At the onset of the disease, recurrent parotid gland enlargement and parotitis is the most common manifestation in children, whereas sicca manifestations are most common in adults.

Cleft lip and Cleft palate

Cleft lip and cleft palate—an opening in the lip or palate—may occur separately or in combination. These deformities originate in the 2nd month of pregnancy, when the front and sides of the face and the palatine shelves fuse imperfectly. Cleft deformities usually occur unilaterally or bilaterally, rarely midline. Only the lip may be involved, or the defect may extend into the upper jaw or nasal cavity.
Cleft lip and cleft palate occur in twice as many males as females; isolated cleft palate is more common in females.

Causes
Cleft lip or palate can occur as part of another chromosomal or Mendelian abnormality (more than 150 have been identified); however, exposure to teratogens during fetal development or a combination of genetic and environmental factors may also produce these defects.
Cleft lip with or without cleft palate occurs in about 1 in 1,000 births among Whites; the incidence is higher among Asians (1.7 in 1,000) and Native Americans (more than 3.6 in 1,000) but lower among Blacks (1 in 2,500). A positive family history is a risk factor for cleft defects.

Signs and symptoms
Congenital defects of the face usually occur in the upper lip. They range from a simple notch to a complete cleft from the lip edge through the floor of the nostril, on either side of the midline, but rarely along the midline itself.

Staphylococcal scalded skin syndrome in Children

A severe skin disorder, staphylococcal scalded skin syndrome (SSSS) is marked by epidermal erythema, peeling, and superficial necrosis that give the skin a scalded appearance. SSSS is most prevalent in infants ages 1 to 3 months but may develop in children; it’s rare in adults.
This disease follows a consistent pattern of progression, and most patients recover fully. Mortality is 2% to 3%, with death usually resulting from complications of fluid and electrolyte loss, sepsis, and involvement of other body systems.

Causes
The causative organism in SSSS is Group 2 Staphylococcus aureus, primarily phage type 71. Predisposing factors may include impaired immunity and renal insufficiency—present to some extent in the normal neonate because of immature development of these systems.

Signs and symptoms
SSSS commonly can be traced to a prodromal upper respiratory tract infection, possibly with concomitant purulent conjunctivitis. Cutaneous changes progress through three stages.

Erythema
In the first stage, erythema becomes visible, usually around the mouth and other orifices, as well as body fold areas, and may spread in widening circles over the entire body surface. The skin becomes tender; Nikolsky’s sign (sloughing of the skin when friction is applied) may appear.

Exfoliation
About 24 to 48 hours later, exfoliation occurs. In the more common, localized form of this disease, superficial erosions and minimal crusting develop, generally around body orifices, and may spread to exposed areas of the skin.
In the more severe forms of this disease, large, flaccid bullae erupt and may spread to cover extensive areas of the body. These bullae eventually rupture, revealing denuded skin.

Severe combined immunodeficiency disease

Both cell-mediated (T-cell) and humoral (B-cell) immunity are deficient or absent in severe combined immunodeficiency disease (SCID). This results in susceptibility to infection from all classes of microorganisms during infancy.

At least three types of SCID exist: 

1. reticular dysgenesis, the most severe type, in which the hematopoietic stem cell fails to differentiate into lymphocytes and granulocytes; 
2. Swiss-type agammaglobulinemia, in which the hematopoietic stem cell fails to differentiate into lymphocytes alone; and 
3. enzyme deficiency, such as adenosine deaminase (ADA) deficiency, in which the buildup of toxic products in the lymphoid tissue causes damage and subsequent dysfunction.

Incidence
SCID affects more males than females; its estimated incidence is 1 in every 100,000 to 500,000 births. Most untreated patients die from infection within 1 year of birth.

Causes
SCID is usually transmitted as an autosomal recessive trait, although it may be X-linked. In most cases, the genetic defect seems associated with failure of the stem cell to differentiate into T and B lymphocytes.
Many molecular defects, such as mutation of the kinase ZAP-70, can cause SCID. X-linked SCID results from a mutation of a subunit of the interleukin-2 (IL-2), IL-4, and IL-7 receptors. Less commonly, it results from an enzyme deficiency.

Protein-calorie malnutrition in Children

Introduction

One of the most prevalent and serious depletion disorders, protein-calorie malnutrition occurs as marasmus (protein-calorie deficiency), characterized by growth failure and wasting; and as kwashiorkor (protein deficiency), characterized by tissue edema and damage. Both forms vary from mild to severe and may be fatal, depending on accompanying stress (particularly sepsis or injury) and duration of deprivation. Protein-calorie malnutrition increases the risk of death from pneumonia, chickenpox, or measles.

Causes
Both marasmus (nonedematous protein-calorie malnutrition) and kwashiorkor (edematous protein-calorie malnutrition) are common in underdeveloped countries and in areas where dietary amino acid content is insufficient to satisfy growth requirements. 

Kwashiorkor typically occurs at about age 1, after infants are weaned from breast milk to a protein-deficient diet of starchy gruels or sugar water, but it can develop at any time during the formative years. 

Marasmus affects infants ages 6 to 18 months as a result of breast-feeding failure or a debilitating condition such as chronic diarrhea.

In industrialized countries, protein-calorie malnutrition may occur secondary to chronic metabolic disease that decreases protein and calorie intake or absorption or trauma that increases protein and calorie requirements. In the United States, protein-calorie malnutrition is estimated to occur to some extent in 50% of surgical and 48% of medical patients. Those who aren’t allowed anything by mouth for an extended period are at high risk for developing protein-calorie malnutrition. Conditions that increase protein-calorie requirements include severe burns and injuries, systemic infections, and cancer (accounts for the largest group of hospitalized patients with protein-calorie malnutrition.) Conditions that cause defective utilization of nutrients include malabsorption syndrome, short-bowel syndrome, and Crohn’s disease.

Signs and symptoms
Children with chronic protein-calorie malnutritioin are small for their chronological age and tend to be physically inactive, mentally apathetic, and susceptible to frequent infections. Anorexia and diarrhea are common.

With acute protein-calorie malnutrition, children are small, gaunt, and emaciated, with no adipose tissue. Their skin is dry and “baggy,” and their hair is sparse and dull brown or reddish yellow. Their temperatures are low; their pulse rates and respirations, slowed. Such children are weak, irritable, and usually hungry; however, they may have anorexia, with nausea and vomiting.

Unlike marasmus, chronic kwashi-orkor allows the patient to grow in height, but adipose tissue diminishes as fat metabolizes to meet energy demands. Edema commonly masks severe muscle wasting; dry, peeling skin and hepatomegaly are common. Patients with secondary protein-calorie malnutrition show signs similar to marasmus, primarily loss of adipose tissue and lean body mass, lethargy, and edema. Severe secondary protein-calorie malnutrition may cause loss of immunocompetence.

Introduction to Encephalitis in Children

Encephalitis is one of the most challenging illnesses in medicine. There are a myriad of potential infectious agents and few specific tests to uncover the culprit. Compounding this diagnostic challenge is the lack of effective therapy for most forms of encephalitis. As polymerase chain reaction (PCR) technology becomes more widely available, our ability to diagnose the various causes of encephalitis will likely improve.

Definition
Encephalitis is an inflammation or infection of the parenchyma of the brain sometimes accompanied by infection of the surrounding tissues (meningoencephelitis), specifically the pia mater, the arachnoid, and the cerebrospinal fluid (CSF).

Causative Agents
Yearly outbreaks of encephalitis occur in the warm months in the United States and usually are associated with insect vectors, such as mosquito-born arboviruses. Eastern equine, Western equine, St. Louis encephalitis, and La Crosse are the most common arboviruses causing encephalitis. By the summer of 2005, West Nile virus had been identified in every state in the continental United States. Although several states documented only avian infections (Washington state, West Virginia, Vermont, New Hampshire, and Maine), it is only a matter of time before the human population is affected. Sporadic cases of herpes simplex encephalitis (HSV) occur year-round and always should be included in the differential of encephalitis, especially since it is one of the few treatable causes of infectious encephalitis. Rickettsial (Rocky Mountain spotted fever; RMSF) and spirochetal (Lyme disease, syphilis) agents may have encephalitis as part of the disease process.

Approach to Chronic Abdominal Pain in Children

Children with chronic abdominal pain account for 5% of all outpatient visits in the pediatric age group. Up to one-third of all children have this complaint, yet less than 10% of these children will have an identifiable organic etiology for their pain. These issues can have great impact on the functioning of the entire family, often causing work absence for the parents, excessive school absence for the child, and feelings of helplessness for the entire family unit.

Definition
Chronic abdominal pain is defined as at least 3 episodes occurring within a 3-month time-span that interferes with normal activity.

Incidence
It is slightly more common in girls than in boys, and usually occurs between the ages of 5 and 12 years. There is an increased incidence of recurrent abdominal pain in the families of these children.

History
The evaluation of a child with chronic abdominal complaints—or for that matter, any problem at all—starts with a comprehensive history. This should start with an interview of the child, as long as he is of the developmental stage in which he can respond to questions with verbal answers. Once exhausting the information available from the child, the parent or caretaker is interviewed. This allows the child to become part of the process, rather than feeling like an excluded object, and generally ensures that you will be able to interview the parent without as much interruption when the child has been asked to speak first.

Two major questions that help separate functional gastrointestinal complaints from disease-based problems are:

1. Does the pain wake you up out of sleep in the middle of the night?
2. Can you point with one finger to the spot that hurts?

Osteosarcoma in Children

Epidemiology.
The annual incidence of osteosarcoma in the USA is 5.6 cases per million children <15 yr of age. The highest risk period for development of osteosarcoma is during the adolescent growth spurt, suggesting an association between rapid bone growth and malignant transformation. Patients with osteosarcoma are taller than their peers of similar age.

Pathogenesis.
Although the cause of osteosarcoma is unknown, certain genetic or acquired conditions predispose patients to development of osteosarcoma.

Patients with hereditary retinoblastoma have a significantly increased risk of developing osteosarcoma. The sites of osteosarcoma in these patients initially were thought to be located only in previously irradiated areas, but more recently they have been shown to arise in sites far from the radiation field. Predisposition to development of osteosarcoma in these patients may be related to loss of heterozygosity of the RB gene.

Osteosarcoma also occurs in the Li-Fraumeni syndrome, which is a familial cancer syndrome associated with germline mutations of the p53 gene.

The pathologic diagnosis of osteosarcoma is made by demonstration of a highly malignant, pleomorphic, spindle cell neoplasm associated with the formation of malignant osteoid and bone.

Clinical Manifestations.
Pain, limp, and swelling are the most common presenting manifestations of osteosarcoma. Because these tumors occur most often in active adolescents, initial complaints may be attributed to a sports injury or sprain; any bone or joint pain not responding to conservative therapy within a reasonable amount of time should be investigated thoroughly. Additional clinical findings may include limitation of motion, joint effusion, tenderness, and warmth. Results of routine laboratory tests, such as a complete blood cell count and chemistry panel, usually are normal, although alkaline phosphatase or lactic dehydrogenase levels may be elevated.

Slipped Capital Femoral Epiphysis

Slipped Capital Femoral Epiphysis is a hip disorder that affects adolescents, most often between 12 and 15 yr of age, and involves the displacement of the CFE from the metaphysis through the zone of hypertrophy layer of the physeal plate.

Classification
SCFE may be classified temporally, according to onset of symptoms (acute, chronic, acute-on-chronic); functionally, according to patient’s ability to bear weight (stable or unstable); or morphologically, as the extent of displacement of the femoral epiphysis relative to the neck (mild, moderate, or severe), as estimated by measurement on radiographic or CT images.

An acute SCFE has been characterized as one occurring in a patient with prodromal symptoms for  appx. 3 wk and should be distinguished from a purely traumatic separation of the epiphysis in a previously normal hip . The patient with an acute slip will usually have some prodromal pain in the groin, thigh, or knee and will usually report a relatively minor injury (a twist or fall) that normally is not as sufficiently violent as to produce an acute fracture of this severity.

Chronic SCFE is the most frequent form of presentation. Typically, an adolescent presents with a few-month history of vague groin, upper thigh, or lower thigh pain and a limp.

The children with acute-on-chronic SCFE may have features of both ends of the spectrum. Prodromal symptoms have been present for >3 wk with a sudden exacerbation of pain.

The stability classification separates patients based on their ability to ambulate and is more useful in predicting prognosis and establishing a treatment plan. The SCFE is considered “stable” when the child is able to walk with or without crutches. A child with an “unstable” SCFE is unable to walk with or without crutches. Patients with unstable SCFEs have a much higher prevalence of osteonecrosis (up to 50%) compared to those with stable SCFEs (nearly 0%). This is most likely due to the vascular injury caused at the time of initial displacement.

Radiographic Findings in Slipped Capital Femoral Epiphysis

Plain Radiography
Plain radiography in anteroposterior and lateral views is the primary and often the only imaging study needed to evaluate a slipped epiphysis. Common radiographic findings include widening and irregularity of the physis, a decrease in epiphyseal height in the center of the acetabulum, a crescent-shaped area of increased density in the proximal portion of the femoral neck, and the “blanch sign of Steel” corresponding to the double density created from the anteriorly displaced femoral neck overlying the femoral head.

In an unaffected patient, the Klein line, a straight line drawn along the superior cortex of the femoral neck on anteroposterior radiograph, intersects the lateral capital epiphysis. As progressive displacement of the epiphysis occurs in SCFE, the amount of the Klein line that intersects the epiphysis decreases, compared with the uninvolved hip, and eventually the line fully misses intersection with the proximal femoral epiphysis . A true lateral (cross-table lateral) radiographic view of the hip better defines the extent of posterior displacement of the femoral epiphysis.

Computed Tomography.
CT can be used to confirm epiphyseal displacement and accurately measure the amount of displacement in patients with symptoms suggestive of an SCFE but without documentation on plain radiographs.

Apnea in New Born

Apnea is a common problem in preterm infants that may be due to prematurity or an associated illness. In term infants, apnea is always worrisome and demands immediate diagnostic evaluation. Periodic breathing must be distinguished from prolonged apneic pauses because the latter may be associated with serious illnesses.

Apnea is a feature of many primary diseases that affect neonates . These disorders produce apnea by direct depression of the central nervous system’s control of respiration (hypoglycemia, meningitis, drugs, hemorrhage, seizures), disturbances in oxygen delivery (shock, sepsis, anemia), or ventilation defects (pneumonia, RDS, persistent pulmonary hypertension of the newborn [PPHN], muscle weakness).

Idiopathic apnea of prematurity occurs in the absence of identifiable predisposing diseases. Apnea is a disorder of respiratory control and may be obstructive, central, or mixed.

Obstructive apnea (pharyngeal instability, neck flexion, nasal occlusion) is characterized by absent airflow but persistent chest wall motion. Pharyngeal collapse may follow the negative airway pressures generated during inspiration, or it may result from incoordination of the tongue and other upper airway muscles involved in maintaining airway patency.

In central apnea, which is caused by decreased central nervous system (CNS) stimuli to respiratory muscles, airflow and chest wall motion are absent. Gestational age is the most important determinant of respiratory control, with the frequency of apnea being inversely related to gestational age. The immaturity of the brainstem respiratory centers is manifested by an attenuated response to carbon dioxide and a paradoxical response to hypoxia that results in apnea rather than hyperventilation. The most common pattern of idiopathic apnea in preterm neonates has a mixed etiology (50–75%), with obstructive apnea preceding (usually) or following central apnea. Short episodes of apnea are usually central, whereas prolonged ones are often mixed.

Clinical features of Kawasaki Disease

Kawasaki disease (KD), formerly known as mucocutaneous lymph node syndrome and infantile polyarteritis nodosa, is an acute febrile vasculitis of childhood.

Kawasaki disease is the leading cause of acquired heart disease in children in the United States and Japan.

Clinical Features

Fever is characteristically high (104°F or higher), remittent, and unresponsive to antibiotics. The duration of fever without treatment is generally 1–2 wk, but it may persist for 3–4 wk. Prolonged fever is prognostic for the development of coronary artery disease.

In addition to fever, the five characteristic features of Kawasaki disease are: bilateral bulbar conjunctival injection, usually without exudate; erythema of the oral and pharyngeal mucosa with strawberry tongue and dry, cracked lips, and without ulceration; edema and erythema of the hands and feet; rash of various forms (maculopapular, erythema multiforme, or scarlatiniform) with accentuation in the groin area; and nonsuppurative cervical lymphadenopathy, usually unilateral, with node size of ?1.5 cm.

Perineal desquamation is common in the acute phase. Periungual desquamation of the fingers and toes begins 1–3 wk after the onset of illness and may progress to involve the entire hand and foot.

Other features include extreme irritability that is especially prominent in infants, aseptic meningitis, diarrhea, mild hepatitis, hydrops of the gallbladder, urethritis and meatitis with sterile pyuria, otitis media, and arthritis. Arthritis may occur early in the illness or may develop in the 2nd–3rd week, generally affecting hands, knees, ankles, or hips. It is self-limited but may persist for several weeks.

Folate Deficiency in Children

Folate exists in a number of different chemical forms. Folic acid (pteroylglutamic acid) is the synthetic form used in fortified foods and supplements. Naturally occurring folates in foods (pteroylpolyglutamate) are not used as well as folic acid. Folate coenzymes are involved in a variety of reactions, including synthesis of deoxyribonucleic acid and purine, amino acid interconversion, and conversion of homocysteine to methionine. Because of its role in protein synthesis, the risk of deficiency is increased during periods of rapid growth or increased cellular metabolism.

Impaired folate status may be associated with long-term drug treatment of various non-neoplastic diseases, including the use of high-dose nonsteroidal anti-inflammatory drugs; the anticonvulsants diphenylhydantoin and phenobarbital; and methotrexate used in the treatment of rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disease.

Folate deficiency may result from poor nutrient intake or poorly prepared foods ; malabsorption (hereditary folate malabsorption, celiac disease, inflammatory bowel disease, alcoholism); diseases with a high cell turnover rate (sickle cell anemia, psoriasis); inborn errors of folate metabolism (methylene tetrahydrofolate reductase, methionine synthase reductase, glutamate formiminotransferase deficiencies) ; or autoantibodies against the cerebral folate receptor in the choroid plexus.

Anemia
Anemia due to decreased folate intake usually becomes manifest under clinical conditions that have increased vitamin requirements (e.g., pregnancy, growth in infancy, chronic hemolysis). The normal infant daily requirement is 25–35microg/day. The anemia is macrocytic (mean corpuscular volume >100 fL). Variations in RBC shape and size are common . The reticulocyte count is low, and nucleated RBCs demonstrating megaloblastic morphology often are seen in the blood. Neutropenia and thrombocytopenia rarely may be present, particularly in patients with long-standing and severe deficiencies. The neutrophils are large, some with hypersegmented nuclei. The bone marrow is hypercellular because of erythroid hyperplasia, and megaloblastic changes are prominent. Large, abnormal neutrophilic forms (giant metamyelocytes) with cytoplasmic vacuolation also are seen.

History And Examination For Skin Disorders

Although many skin disorders are easily recognized by simple inspection, the history and physical examination are often necessary for accurate assessment. 

The entire body surface, mucous membranes, conjunctiva, hair, and nails should always be examined thoroughly under adequate illumination. The color, turgor, texture, temperature, and moisture of the skin and the growth, texture, caliber, and luster of the hair and nails should be noted. 

Skin lesions should be palpated, inspected, and classified on the bases of morphology, size, color, texture, firmness, configuration, location, and distribution. One must also decide whether the changes are those of the primary lesion itself or whether the clinical pattern has been altered by a secondary factor such as infection, trauma, or therapy.

Primary lesions are classified as macules, papules, patches, plaques, nodules, tumors, vesicles, bullae, pustules, wheals, and cysts.

A macule represents an alteration in skin color but cannot be felt.

When the lesion is >1 cm, the term patch is used.

Papules are palpable solid lesions <0.5–1 cm, whereas nodules are larger in diameter.

Tumors are usually larger than nodules and vary considerably in mobility and consistency. Vesicles are raised, fluid-filled lesions <0.5 cm in diameter; when larger, they are called bullae. Pustules contain purulent material.

Treatment Options for SLE in Children

The treatment regimen depends on the affected target organs and disease severity. Sun exposure should be minimized and include use of a sunscreen. Patients are treated to promote clinical well-being, using serologic markers of disease activity as guidelines, including serum complement levels. Nonsteroidal anti-inflammatory agents, used to treat arthralgia and arthritis, are used with caution because patients with lupus are more susceptible to hepatotoxicity. Hydroxychloroquine is often used to treat mild manifestations including skin lesions, fatigue, arthritis, and arthralgia. Hydroxychloroquine may also reduce the risk of thromboembolic disease and lowers lipid levels.

Patients with thrombosis and antiphospholipid antibodies or a lupus anticoagulant should receive anticoagulant medication at least until lupus is in remission. The length of therapy is controversial. Low molecular weight heparin is the anticoagulant of choice; warfarin can also be used.

Corticosteroids control symptoms and autoantibody production in lupus. Treatment with corticosteroids has improved kidney disease and the rate of survival. Corticosteroids can make the diagnosis and treatment of tuberculosis difficult; all patients should have PPD and control skin tests, when possible, before corticosteroids are initiated. The optimal dose and route of administration of corticosteroids are controversial. Patients with systemic disease are often started on 1–2 mg/kg/24 hr of oral prednisone in divided daily doses. When complement levels increase to within the normal range, the dose is carefully tapered to the lowest effective dose. One method uses alternate-day high-dose corticosteroids once disease is controlled to prevent the adverse effects of daily corticosteroid administration. Severely ill patients may require pulse intravenous corticosteroid therapy (30 mg/kg/dose, maximum 1 g/day, given over 60 min, for 3 days). Intermittent high-dose intravenous therapy in combination with low-dose daily oral corticosteroids has been used as an alternative regimen in some centers. Adverse effects of corticosteroids include hypertension, gastritis, cataracts, osteopenia, and cushingoid body habitus.

Introduction to Atrial Flutter in Children

Atrial flutter, also known as intra-atrial re-entrant tachycardia, is a regular or regularly irregular tachycardia characterized by atrial activity at a rate of 250–400 beats/min. These contractions are thought to be due to a re-entrant or circus rhythm originating in the atria and involving a micro-re-entrant loop within the atrial tissue and some form of anatomic obstacle that creates a discontinuity in conduction (fibrosis, surgical suture site, valve annulus). Because the AV node cannot transmit such rapid impulses, some degree of AV block is virtually always present, and the ventricles respond to every 2nd–4th atrial beat. Occasionally, the response is variable and the rhythm appears irregular.

In older children, atrial flutter usually occurs in the setting of congenital heart disease; neonates with atrial flutter frequently have normal hearts.

Clinical Features

Atrial flutter may occur during acute infectious illnesses but is most often seen in patients with large stretched atria, such as those associated with long-standing mitral or tricuspid insufficiency, tricuspid atresia, Ebstein anomaly, or rheumatic mitral stenosis. Atrial flutter can also occur after palliative or corrective intra-atrial surgery. Uncontrolled atrial flutter may precipitate heart failure. Vagal maneuvers (such as carotid sinus pressure or iced saline submersion) or adenosine generally produce a temporary slowing of the heart rate.

Introduction to Hypervitaminosis A

Chronic hypervitaminosis A results from excessive ingestion of vitamin A for several weeks or months.

Toxicity can be induced in adults and children with chronic daily intakes of 15,000 g and 6,000 g, respectively. Symptoms subside rapidly on withdrawal of the vitamin.

Signs of subacute or chronic toxicity may include headache; vomiting; anorexia; dry, itchy desquamating skin; seborrheic cutaneous lesions; fissuring at the corners of the mouth; alopecia and/or coarsening of the hair; bone abnormalities; swelling of the bones; enlargement of the liver and spleen; diplopia; increased intracranial pressure; irritability; stupor; limited motion; and dryness of the mucous membranes. In addition, desquamation of the palms and the soles of the feet is common.

Radiographs show hyperostosis affecting several long bones, especially in the middle of the shafts . Serum levels of vitamin A are elevated. Hypercalcemia and/or liver cirrhosis may be present. Hypervitaminosis A is distinct from cortical hyperostosis.
In young children, toxicity is associated with vomiting and bulging fontanelles. An affected child has anorexia, pruritus, and a lack of weight gain. Acute hypervitaminosis A toxicity has occurred in infants in developing countries after ingestion of very high amounts of vitamin A during vaccine administration. Symptoms include nausea, vomiting, and drowsiness; less common symptoms include diplopia, papilledema, cranial nerve palsies, and other symptoms suggestive ofpseudotumor cerebri. Severe congenital malformations occur in infants of mothers who consumed therapeutic doses (0.5–1.5 mg/kg) of oral 13-cis-retinoic acid during the 1st trimester of pregnancy for treatment of acne or cancer. This results in a high incidence (>20%) of spontaneous abortions and birth defects.

Introduction to Impetigo

A contagious, superficial skin infection, impetigo (also known as impetigo contagiosa) occurs in nonbullous and bullous forms. This vesiculopustular eruptive disorder spreads most easily among infants, young children, and the elderly.

Predisposing factors—such as poor hygiene, anemia, malnutrition, and a warm climate—favor outbreaks of this infection, most of which occur during the late summer and early fall. Impetigo can complicate chickenpox, eczema, and other skin conditions marked by open lesions.

Causes
Coagulase-positive Staphylococcus aureus and group A beta-hemolytic streptococci (or a combination of both) produce epidermal infections.

Signs and symptoms
Common nonbullous impetigo typically begins with a small red macule that turns into a vesicle, becoming pustular with a honey-colored crust within hours. When the vesicle breaks, a thick yellow crust forms from the exudate. Autoinoculation may cause satellite lesions. Other features include pruritus, burning, and regional lymphadenopathy.
A rare but serious complication of streptococcal impetigo is glomerulonephritis.
With bullous impetigo, a thin-walled vesicle opens and a thin, clear crust forms on the subsequent eruption. It commonly appears on exposed areas.

Introduction to Thiamine (Vitamin B1)

Thiamine (vitamin B1) provides the functional group for the coenzyme thiamine pyrophosphate, which is involved in decarboxylation of pyruvate and -ketoglutarate and, thus, is important in the release of energy from carbohydrates. It also participates in the hexose monophosphate shunt that generates nicotinamide adenine dinucleotide phosphate and pentose.

Thiamine also is required for the synthesis of acetylcholine, and deficiency results in impaired nerve conduction.

Good sources of thiamine include meat, legumes, and cereals. Unless enriched, refined cereals and flours have a much lower content of thiamine than whole grains. The vitamin is easily destroyed by heat, particularly in alkaline media, and significant amounts are lost in discarded cooking water. The breast milk of a well-nourished mother provides adequate thiamine; breast-fed infants of thiamine-deficient mothers, however, are at risk for deficiency. Most infants and older children obtain an adequate intake of thiamine from food and do not require supplements.

Thiamine is absorbed efficiently in the gastrointestinal tract, but may be decreased in persons with gastrointestinal or liver disease.

Deficiency (beriberi) has been reported in adolescents after gastric bypass surgery. Intakes in excess of tissue needs are excreted in the urine. Fever and/or stress may increase the requirement for thiamine and unmask marginal thiamine sufficiency, but these factors are unlikely to cause deficiency.