Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 4-6

Four-Month-Old Boy

DEBRA BOYER

PHUONG VO

HISTORY OF PRESENT ILLNESS

The patient is a 4-month-old boy who was a former 28-week premature baby who presented with a 1-week history of a cough. Over the next 4 days, his mother reported an increasing cough with no history of fever or rhinorrhea. He had decreased oral intake and decreased urine output. He had some posttussive emesis and no diarrhea. His uncle has been sick for the last 3 weeks with rhinorrhea and a cough.

MEDICAL HISTORY

The boy born at 28 weeks gestation and required endotracheal intubation for a short period of time after birth. While in the newborn intensive care unit, he did have a course of necrotizing enterocolitis that did not require surgery. He was ultimately discharged home with an apnea monitor and oral caffeine. However, recently his mother ran out of this medication and he had no longer been receiving it. He had two siblings who were healthy.

PHYSICAL EXAMINATION

T 37.2°C; P 138 bpm; RR 27-40/min; BP not obtained; Oxygen saturation 96% in room air and decreasing to 93% with feeds

Weight 25th percentile

On examination, he was alert with moderate respiratory distress and frequent episodes of coughing. His chest examination was significant for grunting with substernal, intercostals, and supraclavicular retractions. Rales were appreciated on the right with good aeration throughout. No wheezes were heard. The remainder of his physical examination was within normal limits.

DIAGNOSTIC STUDIES

The complete blood count revealed a white blood cell count of 25 400 cells/mm3 with 51% lymphocytes, 17% atypical lymphocytes, 25% segmented neutrophils, and 6% monocytes. The hemoglobin was 12.3 gm/dL and the platelet count was 494 000/mm3.

COURSE OF ILLNESS

The patient received an albuterol nebulizer treatment with no significant relief. While in the emergency department, he had frequent episodes of coughing with two episodes complicated by bradycardia to 60 bpm and desaturations to 80%. A chest radiograph was obtained (Figure 4-8). A presumptive diagnosis was made and the appropriate test sent for confirmation of the diagnosis.

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FIGURE 4-8. Chest radiograph.

DISCUSSION CASE 4-6

DIFFERENTIAL DIAGNOSIS

A cough in infancy is most likely related to an infectious process, with viral processes being the leading causes. Respiratory syncytial virus is a common cause of cough. However, other infectious etiologies should always be considered. Even with good adherence to vaccine regimens, bacterial infections such as B. pertussis are still possible in infants. While not commonly expected in this age group, M. pneumoniae infections rarely occur in infancy.

Reactive airway disease, most commonly secondary to viral infections, is also a common cause of cough in infancy. Gastroesophageal reflux should be considered as well, even with often few overt gastrointestinal symptoms.

Less common causes for cough in infancy include congenital malformations, such as tracheoesophageal fistula, tracheobronchomalacia, vascular rings, lobar emphysema, bronchogenic cysts, pulmonary sequestration, laryngeal cleft, and congenital pulmonary airway malformations. Furthermore, one should attempt to elicit a history for any possible swallowing disorder that might lead to recurrent aspiration.

Other less common causes of cough in infancy include cystic fibrosis, congestive heart failure, interstitial pneumonitis, and congenital immunodeficiencies.

This patient’s history is suggestive of an infectious etiology, as he was in good health until approximately 1 week prior to presentation. However, his history of prematurity should add one more disease to the differential diagnosis in this patient, bronchopulmonary dysplasia. These patients are also more likely to develop reactive airways disease in response to a viral infection.

DIAGNOSIS

Chest radiograph revealed bilateral perihilar infiltrates (Figure 4-8). Given the combination of the radiographic findings, worsening cough, dramatic leukocytosis, lymphocytosis with a substantial number of atypical lymphocytes, and contact with an adult with prolonged cough, a presumptive diagnosis of B. pertussis was made. A nasopharyngeal specimen was sent for B. pertussis PCR and was positive. Thus, the diagnosis is infection with B. pertussis.

INCIDENCE AND EPIDEMIOLOGY

Bordetella pertussis, a Gram-negative bacillus, is the causative organism for what is commonly referred to as whooping cough. A whooping cough syndrome can also be seen with B. parapertussisM. pneumoniaeC. trachomatisC.pneumoniae, and some adenoviruses.

Pertussis is considered one of the most highly communicable diseases, with transmission occurring via contact with respiratory tract secretions of an infected patient. With waning immunity from childhood vaccination, adults and adolescents are commonly the source of infection in infants and young children.

The true incidence is unknown as many cases in adolescents and adults are unrecognized. The World Health Organization estimates about 20 to 40 million cases of pertussis per year worldwide, with 90% of the cases occurring in developing countries and 295 000 reported deaths per year. The Centers for Disease Control and Prevention report that in the United States infants less than 1 year of age have the highest incidence with 55.2 cases per 100 000 population although adolescents and adults have the largest increase in incidence rates from 1980 to 2005. In general, the disease is endemic, but there are 3-5 year cycles of epidemics that occur in addition to the endemic levels. For unknown reasons, girls are affected at much higher rates and with higher morbidity than boys.

CLINICAL PRESENTATION

The incubation period is generally 1-3 weeks with the infectious period divided into three stages. The catarrhal stage begins with symptoms of a mild upper respiratory tract infection, and lasts a few days to 1 week. The paroxysmal stage then follows with the characteristic inspiratory whoop. Posttussive emesis is common, and fever is infrequent. In infants, the whoop is generally absent, as they are unable to generate the force needed for this maneuver.

Increased intrathoracic and intraabdominal pressures during coughing may lead to conjunctival and scleral hemorrhages, petechiae on the upper body, epistaxis, and retinal hemorrhages. In infancy, apnea is a common complication with B. pertussis infections. Even young adults can suffer from episodes of laryngospasm. Seizures result from either hypoxia or hyponatremia from inappropriate secretion of antidiuretic hormone secretion.

In most cases, a pertussis infection lasts 6-10 weeks, but it is not uncommon for infants and children to have a persistent cough for 3-4 months following a pertussis infection. This chronic cough lasting for weeks to months characterizes the third stage of pertussis disease progression, the convalescent stage.

Respiratory distress between paroxysms of coughing suggests superinfection with various viruses (adenovirus, respiratory syncytial virus, cytomegalovirus) or bacteria (Streptococcus pneumoniae and Staphylococcus aureus). Other complications include pneumothorax, encephalopathy, and feeding difficulties in infancy. The disease is most severe in infants younger than 1 year of age, especially for premature infants.

DIAGNOSTIC APPROACH

Blood counts. Leukocytosis (white blood cell count >15 000/mm3), usually due to an absolute lymphocytosis, is present in more than 75% of unvaccinated children during the late catarrhal and paroxysmal stages. The degree of lymphocytosis typically parallels the severity of illness. Lymphocytosis is less common and less extreme in previously vaccinated children who develop pertussis. Eosinophilia is uncommon.

Chest roentgenogram. Pulmonary infiltrates are often seen and are most commonly perihilar. Classically, a “shaggy” right heart border is seen but the finding is nonspecific. Peribronchial cuffing or atelectasis may also be observed. Consolidation if present is most likely from a secondary bacterial infection, rarely pertussis pneumonia. Pneumothorax or pneumomediastinum may also be seen as complications of pertussis infection. The chest radiograph should be performed to exclude other cases of cough or respiratory distress, such as pneumonia and congestive heart failure.

Bordetella pertussis culture. Growing the organism in culture is certainly the gold standard for diagnosis. The ability to grow the organism is highest during the catarrhal stage or early paroxysmal stage. A negative culture can be seen in patients who were previously vaccinated, have received pertussis therapy, or have been coughing far beyond the paroxysmal stage.

Direct immunofluorescent assay (DFA). This is performed on nasopharyngeal secretions and has variable sensitivity and low specificity. Furthermore, it requires a significant level of skill and is therefore not very reliable and reproducible.

Polymerase chain reaction (PCR). PCR has been used to document B. pertussis infections even after the organism will no longer grow in culture. Therefore, it is able to detect disease even in the late paroxysmal stage or after patients have received pertussis therapy. This is the preferred method to confirm the diagnosis of pertussis.

TREATMENT

As young infants with pertussis have a high risk for complications, there should be a low threshold for admitting these patients. Many of these infants will require intensive care unit admission to monitor for apneic episodes and neurologic sequelae.

Infants should be treated with a macrolide antibiotic, including erythromycin, azithromycin, and clarithromycin. Erythromycin is the most common choice. For infants less than 1 month of age, the AAP and CDC recommend the use of azithromycin. Erythromycin is the alternative; clarithromycin is not recommended. Azithromycin has fewer adverse side effects than erythromycin, which has been associated with the development of infantile hypertrophic pyloric stenosis. Trimethoprim-sulfamethoxazole is an alternative agent that can be used for children older than 2 months of age who cannot take macrolides for pertussis treatment or prophylaxis or who are infected with a macrolide-resistant strain.

The length of antimicrobial therapy is generally recommended to be 14 days. For the newer macro-lides, azithromycin and clarithromycin, treatment course can be shorter (5-7 days). There is some controversy as to whether antibiotics administered during the catarrhal stage will decrease disease severity. However, antibiotics should still be administered, even in the paroxysmal stage, as this will limit the spread of the disease to others. Additionally, studies are underway assessing the efficacy of pertussis immune globulin as an adjunctive therapy in extremely ill infants.

Antibiotic prophylaxis is recommended for all household and close contacts and generally consists of 10-14 days of erythromycin. Azithromycin for 5 days or clarithromycin for 7 days can also be used for postexposure phrophylaxis. Certainly, prevention is essential to limit morbidity and mortality from pertussis. The acellular pertussis vaccine is currently the recommended form and is administered in combination with diphtheria and tetanus toxoids (DTaP). It is recommended that children receive five doses prior to school-entry.

SUGGESTED READINGS

1. American Academy of Pediatrics. Pertussis. In: Pickering LK, Baker CJ, Kimberlin MD, Long SS, eds. 2009 Red Book: Report on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:504.

2. Hewlett EL. Bordetella species. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:2414-2419.

3. Hoppe JE. Neonatal pertussis. Pediatr Infect Dis J. 2000; 19:244-247.

4. Long SS, Edwards KM. Bordetella pertussis (pertussis) and other species. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 2nd ed. New York: Churchill Livingstone; 2003:880-888.

5. Senzilet LD, Halperin SA, Spika JS, et al. Pertussis is a frequent cause of prolonged cough illness in adults and adolescents. Clin Infect Dis. 2001;32:1691-1697.

6. Sprauer MA, Cochi SL, Zell ER, et al. Prevention of secondary transmission of pertussis in households with early use of erythromycin. Am J Dis Child. 1992; 146:177-181.