DEFINITION OF THE COMPLAINT
Syncope is generally thought of as a temporary, but sudden, loss of consciousness and postural tone. It is due to a reversible interruption of cerebral perfusion, typically caused by a deficit of cerebral oxygen or glucose delivery. The deficit in oxygen delivery may be caused by decreased cardiac output, peripheral vasodilatation, or obstruction of cerebral blood flow. It is important to differentiate the episode of syncope from other etiologies that appear like syncope, such as seizure and near syncopal episodes. Painful events, episodes of micturition or defecation, and stress frequently precede syncope. Sweating and nausea prior to the episode are common as well. Seizures frequently have no prodromal period; however, they may be associated with an aura prior to the event. Seizures are frequently associated with tonic-clonic movements during the event; however, syncopal events that last 20 seconds or longer can also be associated with very brief tonic-clonic movements. Confusion after the event, prolonged return to normal state of consciousness, and unconsciousness lasting longer than 5 minutes suggests seizure activity. During near syncopal episodes the patient feels as though they are about to lose consciousness, but do not actually become unconscious.
Syncope is a common complaint in pediatrics. Approximately 15% of children will have a syncopal episode by the time they reach adulthood.
COMPLAINT BY CAUSE AND FREQUENCY
Pediatric causes of syncope are generally benign, but syncope may signal serious life-threatening causes, particularly if it is recurrent or if there is a family history of sudden cardiac arrest. In children, common causes of syncope include vasovagal episodes, orthostatic hypotension, and breath-holding spells (Table 18-1). In contrast, most adult syncope is due to a cardiac cause. The goal in evaluating syncope is to differentiate benign causes from a more worrisome etiology (Table 18-2).
TABLE 18-1. Differential diagnosis by age.
TABLE 18-2. Differential diagnosis of syncope by etiology.
• Were there any palpitations or “funny heart beats”?
—If the child reports palpitations, then a cardiac dysrhythmia should be considered.
• Did it occur with activity?
—Syncope that occurs with activity is particularly concerning for idiopathic hypertrophic cardio-myopathy.
• Did it occur without warning?
—Syncope that occurs suddenly and without warning should raise concern for a cardiac arrhythmia.
• Were there prodromal symptoms?
—Acute orthostatic intolerance (e.g., simple faint) typically occurs in the context of known precipitants (e.g., standing, heat, emotion) and prodromal symptoms (e.g., nausea, blurred vision, headache).
• Did it happen on standing?
—Orthostatic hypotension is associated with syncope on standing.
• Was there pain, fear, or some disturbing visual sight prior to the syncope?
• Was there any seizure-like activity?
—Brief seizure-like motor activity can occur with vasovagal syncope. Prolonged seizure activity should prompt a more thorough seizure workup. There is no significant postictal period with the seizure-like activity associated with syncope.
• How long did it take to return to baseline?
—Vasovagal syncope is associated with a relatively quick (minutes) return to baseline mental status as soon as cerebral blood flow is restored. If there is a delay in assuming a recumbent position, there may be a longer delay in return to baseline mental status. Increased duration of unconsciousness or confusion suggests seizures rather than syncope.
• Was there a history of trauma?
—A recent history of head trauma raises concern for intracranial hemorrhage.
• Is there a family history of sudden death, including common causes such as drowning or auto accidents?
—A family history of sudden death should raise suspicion for cardiac arrhythmias.
• Is there a history of anemia?
—Anemic patients may be more likely to have a syncopal episode because of decreased cerebral oxygen delivery.
HISTORY OF PRESENT ILLNESS
A 17-year-old girl presented to the emergency department after her second episode of passing out in a week. The first episode happened 7 days ago while she was walking home from school. She experienced a prodromal period of everything around her blackening and then awoke on the sidewalk with her friends around her. Her friends took her home that day. The next episode occurred shortly prior to presentation. She had just finished dinner and was walking into another room when a similar episode of darkening occurred and then she awoke on the floor. On review of systems, she was found to have had occasional episodes of shaking chills, tactile temperatures, and a 5-lb weight loss during a 2-week period. She was a senior in high school and planning on going to college. She was sexually active, but used protection every time. Her last menstrual period, which occurred 1 week ago, was normal.
The girl has been a healthy child and had never been hospitalized. She has three brothers who are also healthy. Her immunizations were up-to-date, including the human papilloma virus vaccine.
T 38.2°C; HR 90 bpm; RR 20/min; BP 95/58 mmHg
Weight 75th percentile and Height 20th percentile
On examination she was alert and cooperative in no distress. She did not appear pale. Her head and neck examination was normal. Her lungs were clear to auscultation. Her cardiac examination was normal. Her abdomen was soft and there was no organomegaly or masses detected. Her neurologic examination was normal. Her skin examination revealed rashes all over her body (Figure 18-1).
FIGURE 18-1. Photo of patient’s rash.
A complete blood count revealed a WBC count of 12 000 cells/mm3 (6% bands, 30% segmented neutrophils, 42% lymphocytes, 19% atypical lymphocytes, 3% monocytes), hemoglobin of 12.2 g/dL, and a platelet count of 14 000/mm3.
COURSE OF ILLNESS
She was admitted to the hospital for further evaluation. Due to the thrombocytopenia, fever, and weight loss, a bone marrow aspirate was performed.
The presence of intermittent fever, petechial rash, thrombocytopenia, and 5-lb weight loss raise concern for neoplastic disorders, such as leukemia or lymphoma. Blast forms on peripheral smear are occasionally mistaken for atypical lymphocytes. However, they are also a marker for a potential Epstein-Barr virus (EBV) infection. More broadly, thrombocytopenia may be caused by increased platelet destruction or consumption or by impaired or ineffective platelet production. Infectious causes of platelet destruction include EBV, cytomegalovirus, human immunodeficiency virus, hepatitis B or C, toxoplasmosis, leptospirosis, syphilis, rickettsioses (e.g., Rocky Mountain spotted fever, ehrlichiosis, human granulocytic anaplasmosis), and bacterial sepsis. Idiopathic thrombocytopenic purpura is a frequent cause of thrombocytopenia in children that can have both an acute and chronic course. However, the incidence of ITP peaks at 3-5 years of age. Other immunologic causes of platelet destruction include systemic lupus erythematosus, autoimmune hemolytic anemia (Evan syndrome), and hyperthyroidism. Nonimmunologic causes include hemolytic-uremic syndrome and Kasabach-Merritt syndrome. Drug-induced thrombocytopenia should be considered if the patient is taking any medication, particularly sulfonamides, digoxin, quinine, quinidine, or chemotherapeutic agents. Disorders of impaired platelet production include marrow infiltrative processes such as leukemias, nutritional deficiencies (e.g., iron, folate, vitamin B12), and infection-associated suppression (e.g., EBV, HIV, parvovirus B9). Thrombocytopenia can occur after vaccination with MMR vaccine. Rare genetic disorders such as Fanconi anemia, Hermansky-Pudlak syndrome, thrombocytopenia with absent radii syndrome (TAR), Wiskott-Aldrich syndrome, May-Hegglin anomaly, and Bernard-Soulier disease are possibilities as well.
The petechial rash was consistent with her thrombocytopenia (Figure 18-1). The bone marrow aspirate revealed a normal marrow with increased megakaryocytes. The interpretation is that this is a clinical picture consistent with viral consumption of platelets. The EBV titers were positive for IgM and IgG antibody to viral capsid antigen. No Epstein-Barr nuclear antigen (EBNA) was detected. The diagnosis is EBV infection.
INCIDENCE AND EPIDEMIOLOGY
EBV is close to ubiquitous. It infects more than 90% of the population and persists for the lifetime of the host. Infection occurs at a later age in developed countries than in developing countries. This differential may be due to improved sanitary conditions and reduced population density in developed countries. The incidence of EBV infection is 50 per 100 000 individuals overall; however, it is 1 per 1000 individuals aged 15-25 years. The incubation period may last up to 30 days.
EBV is linked to infectious mononucleosis, Burkitt lymphoma, nasopharyngeal carcinoma, as well as other cancers. The virus is a member of the herpesvirus family. EBV binds to the CD21 molecule on the B-cell and gains entry into the cell. After infection of an epithelial cell in the oropharynx, the virus replicates and the cell ultimately dies. When EBV infects the B-cell, the virus becomes latent. However, unlike other herpes-virus infections, EBV does not recur. Infection is spread from person to person with contact of oral secretions. Transmission by aerosol or fomites is uncommon. The incubation period during which the virus may be communicated but the patient is asymptomatic is approximately 4 weeks; however, transmission rates are relatively low as evidenced by the absence of widespread EBV epidemics.
Young children with EBV exhibit no or few symptoms. Symptoms, when present, typically mimic viral respiratory infections with fever, cough, and rhinitis. While acute EBV infection is not synonymous with infectious mononucleosis (“mono”), infectious mononucleosis is the most commonly recognized clinical manifestation of EBV infection. Infectious mononucleosis typically presents with the triad of fever, tonsillopharyngitis, and lymphadenopathy. The pharyngitis is typically exudative. Lymphadenopathy is nontender and symmetrically involves the posterior cervical chains. Nausea, vomiting, and anorexia frequently occur which likely reflects the high prevalence of hepatitis (90% of patients may have a mild hepatitis). More than half of all patients with EBV infection will have splenomegaly; however, hepatomegaly is much less frequent. The acute symptoms resolve within 2 weeks, though fatigue may persist longer.
A minority of patients will have rashes which may be petechial, maculopapular, scarlatiniform, or urti-carial. Other less common systemic presentations of EBV infection include Guillain-Barré syndrome, facial nerve palsy, aseptic meningitis, meningoen-cephalitis, metamorphopsia (“Alice in Wonderland” syndrome in which there are bizarre perceptual distortions in shape or spatial relationships), transverse myelitis, peripheral neuropathy, optic neuritis, hemophagocytic lymphohistiocytosis, and, in boys, orchitis.
Complications from EBV infection include the possibility of a diffuse morbilliform rash if the patient is administered a penicillin drug, splenic rupture, upper airway obstruction, and lympho-proliferative disorders. Splenic rupture, which is more common in boys, has been reported to occur in 1 in 1000 cases typically on day 4-21 after the onset of symptoms. It may occur spontaneously and should be considered in any patient with left upper abdominal pain that radiates to the left shoulder. Airway obstruction is very rare, but carries significant morbidity and mortality. The airway compromise can be treated with steroids if necessary. Lymphoproliferative disorders can occur if there is decreased cellular immunity. It is the T-cell and natural killer cells that keep the latent EBV infection in check.
The diagnosis of an EBV infection is based on the correct clinical picture with supporting laboratory evidence.
Complete blood count. The complete blood count typically reveals a leukocytosis, though neutropenia is relatively common; the differential count usually reveals lymphocyte predominance with greater than 10% atypical lymphocytes. Other viruses that cause atypical lymphocytes include cytomegalovirus, human immunodeficiency virus, hepatitis, and measles; however, only EBV and cytomegalovirus have greater than 10% atypical lymphocytes. Mild thrombocytopenia is common; the platelet count rarely decreased below 100 000 platelets/mm3. Anemia is typically not associated with EBV, but if present consider autoimmune hemolysis (which occurs in less than 1% of patients) or splenic rupture.
Hepatic transaminases. Hepatic transaminases may be mildly elevated (two- to threefold).
Heterophile antibodies. Heterophile antibodies (e.g., Monospot), which agglutinate sheep or horse red blood cells, may be positive. These antibodies typically appear within 2 weeks of infection and may persist for as long as 6 months. Younger children are less likely than older children to have heterophile antibodies. False-positive monospot results may occur with leukemia, lymphoma, and Gaucher disease.
EBV-specific antibodies. EBV antibody titers may be sent for confirmation of disease. IgM and IgG antibodies directed against viral capsid antigen (anti-VCA IgM and IgG) appear first and are always present during the symptomatic phase (Table 18-3). The IgM is transient, disappearing within 2-3 months, while the IgG antibodies persist. Antibodies against EBV early antigen (anti-EA) typically increase several weeks after infection and disappear by 12 months. Anti-Epstein-Barr virus nuclear antigen antibody (anti-EBNA) appears last (usually >6 weeks after infection) and persists indefinitely. The presence of anti-EBNA antibodies excludes the possibility of acute infection.
TABLE 18-3. Interpretation of Epstein-Barr virus antibodies.
EBV polymerase chain reaction. EBV polymerase chain reaction (PCR) has limited utility in the acute infectious stage. It may be transiently positive in acute infections, but it is also usually positive in those who have had a past EBV infection in whom the current symptoms may be unrelated to EBV. It is most useful in immune compromised hosts at risk for lymphoproliferative disorder.
The mainstay of treatment is supportive care including adequate rest, fluids, and antipyretics. Although antivirals such as acyclovir demonstrate in vitro activity against EBV, there is no clinical benefit in uncomplicated mononucleosis in an otherwise healthy child. In the absence of concurrent bacterial infection, antibiotics should not be used. If antibiotic therapy is necessary, aminopenicillins (e.g., amoxicillin, ampicillin) should be avoided as these agents cause a rash, typically manifesting after the first few days of therapy. The rash is maculopapular, pruritic, and prolonged. Its appearance is not a contraindication to future aminopenicillin use. Systemic corticosteroids are not routinely recommended, but can be considered when there are complications such as tonsillar hypertrophy causing airway obstruction, massive splenomegaly, myocarditis, pericarditis, or significant hemolysis. Because of the possibility of splenic rupture, patients should avoid contact sports for at least 1 month or until the resolution of the splenomegaly.
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HISTORY OF PRESENT ILLNESS
A 15-year-old boy felt the acute onset of his heart beating fast while he was on the phone with a friend. He became dizzy and lightheaded and fell backward onto his bed. He was not sure whether he lost consciousness, but remembered calling for his mother to help him. He was taken to the community emergency department for assistance. On arrival, he had some mild mid-sternal chest pain. He denied fever, nausea, vomiting, diarrhea, and cough. The remainder of his review of systems was negative.
He has been a healthy child with no significant illnesses. He was a good student at school and active in sports. His family history did not reveal any episodes of sudden unexplained death. Of note, his sister had coarctation of the aorta that required repair in infancy. He did not take any medications. He has received all of his childhood immunizations.
T 37.2°C; HR 230 bpm; RR 20/min; BP 105/68 mmHg
Weight 50th percentile and Height 90th percentile
On examination he was awake, but anxious appearing. His head and neck examination was normal. His lungs were clear to auscultation. His cardiac examination was significant for profound tachycardia with a rate that could not be counted manually. There was no jugular venous distention. His perfusion was adequate with a capillary refill of 1 second at the fingertip. His pulses were palpable throughout. His abdomen was soft without any enlargement of his spleen or liver. His extremities were well perfused. His neurologic examination was normal.
WBC count revealed 12 400 cells/mm3 (54% segmented neutrophils, 1% bands, 38% lymphocytes); hemoglobin, 13.2 g/dL; and platelets, 278 000/mm3. Measurement of serum chemistries revealed the following: sodium, 138 mEq/L; potassium, 4.3 mEq/L; chloride, 106 mEq/L; bicarbonate, 22 mEq/L; calcium, 9.2 mg/dL; and magnesium, 2.9 mg/dL.
COURSE OF ILLNESS
Chest roentogram (CXR) revealed a normal heart size and no pulmonary edema. The initial (Figure 18-2A) and subsequent (Figure 18-2B) electrocardiograms (ECG) revealed the acute and underlying diagnoses.
FIGURE 18-2. A. Initial ECG. B. Subsequent ECG.