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

CASE 2-3

Three-Month-Old Girl

MEGAN AYLOR

HISTORY OF PRESENT ILLNESS

A 3-month-old female presented to the emergency department with several days of increasing fussiness and poor feeding. The infant has always breastfed well; however, three days prior to admission the infant developed a weak suck and difficulty breastfeeding. Although the number of wet diapers had not changed, they have been less saturated, and the baby has had no bowel movement during the previous four days. The parents related that the child’s cry was not as loud as usual. The infant was evaluated by his pediatrician and referred to the emergency department. There has been no history of fever, vomiting, or diarrhea. There have been no ill contacts.

MEDICAL HISTORY

The infant has been healthy until this past week. Pregnancy and delivery were uncomplicated. There is a family history of pyloric stenosis in the father. A 2-year-old sibling is healthy.

PHYSICAL EXAMINATION

T 37.4°C; HR 156 bpm; RR 30/min; BP 100/80 mmHg

Weight and Height 50th percentile

On examination she was alert, but had a weak cry. Her head and neck examination was remarkable for bilateral ptosis and decreased facial expression. Cardiac and pulmonary examinations were normal. Her abdomen was distended but soft. On neurologic examination, she had a weak gag and poor tone. Her deep tendon reflexes were intact.

DIAGNOSTIC STUDIES

Laboratory testing revealed a white blood cell count of 10 100 cells/mm3 (33% segmented neutrophils, 56% lymphocytes, 8% monocytes); hemoglobin, 11.7 g/dL; platelets, 490 000/mm3; sodium, 139 mmol/L; potassium, 4.9 mmol/L; chloride, 106 mmol/L; carbon dioxide, 18 mmol/L; blood urea nitrogen, 12 mg/dL; creatinine, 0.3 mg/dL; and glucose, 58 mg/dL. A negative inspiratory force was measured at 20 cmH2O.

COURSE OF ILLNESS

Intravenous glucose and normal saline were administered in the emergency department. The patient ultimately required endotracheal intubation due to inability to protect her airway. Her appearance combined with historical features suggested a diagnosis that was confirmed by additional testing.

DISCUSSION CASE 2-3

DIFFERENTIAL DIAGNOSIS

The diagnostic possibilities in this child with decreased activity and hypotonia include neurologic conditions that involve either the upper motor neuron (cerebral cortex and spinal cord) or lower motor neuron (anterior horn cell, peripheral nerve, neuromuscular junction, or the muscle) (Table 2-3). Upper motor diseases, such as stroke, hemorrhage, and transverse myelitis, are possibilities. Lower motor diseases include poliomyelitis, spinal muscular atrophy, Guillain-Barré syndrome, congenital myasthenia gravis, botulism, and muscular dystrophies. Infectious etiologies such as overwhelming sepsis should be considered; however, lack of a fever makes these less likely. Ingestions can cause weakness, particularly barbiturates. Inborn errors of metabolism should be considered as well. Chromosomal disorders such as Down syndrome, Prader-Willi syndrome, achondroplasia, familial dysautonomia, and trisomy 13 may present with hypotonia as an early clinical feature; however, the acute onset in this case makes these diagnoses unlikely. The history of weakness, decreased feeding, weak cry, and constipation is a classic presentation of infant botulism.

TABLE 2-3. Causes of hypotonia in an infant.

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DIAGNOSIS

The infant had significant hypotonia but was not tachycardic or hypotensive. An electromyogram (EMG) was obtained to assist with confirmation of the suspected diagnosis of infantile botulism. The EMG revealed a 56% incremental response that is consistent with a presynaptic neuromuscular junction disorder. The pattern is consistent with infantile botulism. Furthermore, stool studies isolated the botulinum toxin, type B. The diagnosis of infant botulism was made.

INCIDENCE AND EPIDEMIOLOGY

Up to 170 cases of botulism are reported in the United States annually, and the majority of cases are due to infant botulism. Although the disease has been reported in all 50 states, it is most common in California, Pennsylvania, and Utah. Unlike the adult form of botulism, which occurs after the ingestion of preformed toxin, infantile botulism occurs after the ingestion of Clostridium botulinum spores, found in soil and honey. Spores then germinate in the intestine, colonize the intestinal tract, and the organism produces toxin. The botulinal toxin, one of the most potent neurotoxins, irreversibly binds to the presynaptic cholinergic receptors and prevents the release of acetylcho-line at the neuromuscular junction, leading to a descending flaccid paralysis.

CLINICAL PRESENTATION

The average age at onset is 10 weeks, with a range of 10 days to 7 months. Patients present subacutely with constipation and symptoms associated with cranial nerve palsies, including a weak suck, poor feeding, and subsequent irritability. As paralysis descends over subsequent days, patients develop head lag and generalized weakness. On physical examination, patients are hypotonic and hyporeflexic, with ptosis, poor head control, and diminished suck, gag, and respiratory effort. Mental status is not directly affected; however, infants are often irritable due to inability to feed well. Respiratory compromise is common; 70% of patients with infantile botulism will develop respiratory failure requiring mechanical ventilation. Patients may also have autonomic dysfunction manifested by decreased intestinal motility, distended urinary bladder, decreased tear production, decreased saliva production, periodic flushing and sweating, as well as fluctuations in their heart rate and blood pressure. Complications of therapy such as nosocomial infections may occur as a result of supportive care interventions.

DIAGNOSTIC APPROACH

Typically, the diagnosis is made on a clinical basis using the history and physical examination findings.

EMG. EMG can be helpful in making the diagnosis, particularly if an incremental response is found. Brief, small amplitude, overly abundant motor unit potentials suggest the diagnosis of infant botulism. If infant botulism is highly suspected and initial EMG testing is negative, repeat testing in 1-2 days is warranted.

Stool studies. Although results of stool testing are not immediately available, it is helpful to confirm the diagnosis by detection of botulinum toxin.

TREATMENT

Providing respiratory and nutritional supportive care, often in the ICU setting, is the mainstay of treatment. Because the disease is toxin mediated, antibiotics are not effective; in fact, aminoglyco-sides may worsen the paralysis by potentiating the neuromuscular blockade.

The development of human botulism immune globulin (BIG) has made a substantial impact on outcomes. When given within 3 days of hospitalization, BIG is shown to decrease duration of hospitalization, length of mechanical ventilation, ICU length of stay, and length of nasogastric tube feedings. The cost of hospitalization is reduced by half, offsetting the high cost of the therapy. Therefore, BIG should be initiated promptly when infant botulism is diagnosed clinically. Therapy should not be delayed while awaiting confirmatory stool studies.

Regeneration of the motor endplates takes weeks, often with waxing and waning clinical symptoms. However, patients generally survive with full neurologic recovery.

SUGGESTED READINGS

1. Frankovich TL, Arnon SS. Clinical trial of botulism immune globulin for infant botulism. Western J Med. 1991;154:103.

2. Long SS, Gajewski JL, Brown LW, Gilligan PH. Clinical, laboratory, and environmental features of infant botulism in Southeastern Pennsylvania. Pediatrics. 1985; 75:935-941.

3. Wigginton JM, Thill P. Infant botulism: a review of the literature. Clin Pediatr. 1993;32:669-674.

4. Cox N, Hinkle R. Infant botulism. Am Fam Phys. 2002; 65(7):1388-1392.

5. Underwood K, Rubin S, Deakers T, Newth C. Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Children’s Hospital Los Angeles. Pediatrics. 2007;120(6):e1380-e1385.