HISTORY OF PRESENT ILLNESS
An 11-month-old male was brought to the emergency department because of decreased activity level. He had a 3-day illness consisting of fever to 39°C and four episodes of nonbloody diarrhea each day. There was no history of emesis. On the day of presentation, despite drinking four 8-ounce bottles of an oral rehydration solution, he had decreased urine output. He also refused to play and instead wanted to lie down and rest. The mother called the paramedics when she felt that he was difficult to arouse.
The boy’s prenatal and birth histories were normal. He had a history of wheezing with an upper respiratory infection at 3 months of age. He had no hospitalizations or surgeries. He was taking medications and had no allergies. His immunizations were current.
T 40.3°C; HR 183; RR 46/min; BP 99/41 mmHg
Weight and Height 75th percentile
On examination, he was lethargic and minimally responsive to painful stimuli. The head and neck examination did not reveal any signs of external trauma. His gaze was disconjugate, but his pupils were reactive from 3 mm to 2 mm bilaterally. He had sunken eyes and dry mucous membranes. Respiratory examination revealed shallow, labored respirations with moderately increased work of breathing. He had intercostal and substernal retractions as well as abdominal breathing. Breath sounds were coarse to auscultation. Cardiac examination was significant for tachycardia without murmur or abnormal heart sounds. Abdominal examination revealed hypoactive bowel sounds but no tenderness, hepatosplenomegaly, or palpable masses. Rectal examination revealed gross blood. Neurologic examination was significant for overall hypotonia and unresponsiveness to voice or painful stimuli. His lower extremity deep tendon reflexes were 2+ and symmetric. He had an intact gag reflex and downgoing Babinski reflexes. The patient had a rash (Figure 2-3).
FIGURE 2-3. Photograph of a rash.
In the emergency department, blood, urine, and CSF studies and cultures were obtained. Additional laboratory studies revealed a white blood cell count of 13 400 cells/mm3, with 11% bands, 63% segmented neutrophils, 34% lymphocytes, and 2% monocytes. Hemoglobin was 6.6 g/dL; platelets, 195 000/mm3; sodium, 131 mmol/L; potassium, 5.8 mmol/L; chloride, 101 mmol/L; carbon dioxide, 18 mmol/L; blood urea nitrogen, 19 mg/dL; creatinine, 0.7 mg/dL; and glucose, 57 mg/dL. His prothrombin time (PT) was prolonged at 16.4 seconds (reference range, 10-12 seconds) and his activated partial thromboplastin time (PTT) is 29.1 seconds (reference range, 30-45 seconds). CSF studies revealed a gram stain significant for few white blood cells, a cell count of 100 WBCs/uL (65% neutrophils), glucose of 40 mg/dL, and protein 90 mg/dL. CT of the head was also normal. Serum and urine toxicology screens were negative.
COURSE OF ILLNESS
Patient was placed on 100% oxygen and provided with 40 mL/kg normal saline bolus and broad-spectrum antibiotics. A nasogastric tube was placed given the possibility of an upper GI bleed, and coffee-ground material was aspirated from the stomach. Given the findings of gross rectal blood, coffee-ground gastric contents, hypoactive bowel sounds, and low hemoglobin, the pediatric surgery staff was consulted in the emergency department on suspicion of an intraabdominal catastrophe, particularly intussusception or volvulus. He received broad-spectrum antimicrobial agents and was immediately taken to the operating room for an exploratory laparotomy which did not reveal volvulus or intussusception. The patient’s rash suggested a specific etiology (Figure 2-3).
DISCUSSION CASE 2-4
The differential diagnosis centers around two primary concerns. The first is an infectious etiology, including bacteremia, pneumonia, pyelonephritis, pyelonephrosis, or meningitis. In this particular case, the patient had blood, urine, and CSF studies performed to evaluate for infection and had broad spectrum antibiotics started. The low hemoglobin, hypoactive bowel sounds, and bright red blood from rectum make an abdominal process very concerning. This may include trauma (accidental or nonaccidental) or other causes of lower gastrointestinal bleeding (intussusception, malrotation with volvulus, meckel’s diverticulum, henoch schönlein purpura, or some type of coagulopathy). In this particular case, the patient was taken into operating room for laparotomy to evaluate for a surgical abdominal emergency. However, the laparotomy was negative.
The patient’s diffuse purpuric lesions suggested bacterial sepsis due to Neisseria meningitidis (Figure 2-3). His blood and CSF cultures ultimately grew N. meningitidis. The diagnosis is meningococcal meningitis and sepsis.
INCIDENCE AND EPIDEMIOLOGY
Neisseria meningitidis (meningococcus) is a Gram-negative diplococcus that causes bacteremia and meningitis. Meningococcus is a major burden worldwide, causing an estimated 170 000 deaths per year. There are 13 sero-groups; however, B, C, and Y are the three sero-groups most frequently implicated in the United States, each accounting for about 30% of systemic disease.
Neisseria meningitidis is a component of the normal flora of the upper respiratory tract, which is the only reservoir for the organism. Transmission occurs via the respiratory secretions and by person-to-person contact. Approximately 2.5% of children and 10% of the general population are asymptomatic carriers. Carriage rates have been shown to be higher in institutions, including universities, schools, prisons, and the military. In one study, 32.7% of persons between the ages of 20 and 24 years were asymptomatic carriers. Peak rates of infection occur between November and March. The incubation period is most commonly less than 4 days, but can be as long as 10 days. Fifty percent of cases of meningococcemia occur in children less than 2 years old. However, during epidemics, there is a shift in incidence toward older children, adolescents, and young adults. Factors associated with meningococcal infection include anatomic or functional asplenia and complement deficiency.
The disease caused by N. meningitidis varies from asymptomatic transient bacteremia to fulminant sepsis and death. Pathogenic N. meningitidis colonizes the respiratory tract and may invade the bloodstream. The patient becomes bacteremic and progressively sicker. The bacteremia may seed the meninges causing meningitis. Those patients who present with meningitis have a better prognosis than patients with bacteremia alone. Shortly after the administration of appropriate antibiotics, some patients have a marked clinical deterioration, ranging from hypotension to death. This deterioration is thought to be caused by stimulation of the host inflammatory pathway by endotoxin (a component of the gram negative bacterial cell wall). Meningococcal disease can lead to death in as few as 12 hours with 50% of deaths occurring within 24 hours of presentation. Invasive infection usually results in meningococcemia, meningitis, or both. However, it can infect any organ, including the myocardium, adrenals, lungs, and joint spaces. Approximately 55% of patients with meningococcal disease have meningitis. Additionally, 50% of patients have positive blood cultures.
A history of a preceding URI can often be elicited from patients with meningococcemia. The onset of illness is abrupt, with fever, lethargy, and rash. The rash is typically petechial and can progress rapidly to purpura due to a disseminated coagulopathy. Some patients develop fulminant meningococcemia with disseminated intravascular coagulopathy, shock, and myocardial dysfunction. Fulminant disease can be further complicated by adrenal hemorrhage (Waterhouse-Friderichsen syndrome), leading to rapidly progressive adrenocortical insufficiency and shock. There is a 20% mortality rate in cases of fulminant disease.
The prompt diagnosis of meningococcal disease requires a high index of clinical suspicion. Recovery of the organism from a normally sterile site provides the definitive diagnosis.
Appropriate cultures. The organism can be isolated from blood, CSF, and scrapings from the petechial rash. Blood cultures are positive in about 50% of patients with presumed meningococcal disease. Because the organism is a normal component of the nasopharynx, nasopharyngeal cultures are not helpful.
Other studies. PCR may be useful in the rapid diagnosis of meningococcal disease, particularly in patients who have been pretreated with antibiotics. Gram stain of the blood, CSF, or skin scrappings is also useful for the rapid detection of meningococci. Other laboratory studies that may affect management include serum electrolytes, prothrombin time, and partial thromboplastin times.
Treatment of suspected cases of meningococcal infection should be administered as early as possible in the course of the disease, and antibiotic administration should not be delayed while waiting for a lumbar puncture. The initial antimicrobial coverage of meningococcal infections should be a third-generation cephalosporin, such as cefotaxime or ceftriaxone. Chloramphenicol, although rarely used, is appropriate for patients with anaphylactoid reactions to penicillins or cephalosporins. Although most isolates in the United States are sensitive to penicillin, penicillin-resistant isolates, first identified in Spain in 1987, are prevalent in Spain, Italy, and parts of Africa. In the United States, routine susceptibility testing is not indicated. Five to seven days of therapy is adequate for most cases of invasive meningococcal disease. Glucocorticoids have not been shown to be beneficial in the management of meningococcal disease. Treatment with heparin and other anticoagulants remain controversial. Aggressive fluid resuscitation and inotropic support are necessary for maintaining adequate perfusion in cases of septic shock.
Chemoprophylaxis is indicated for individuals who have been exposed to the index case within seven days prior to the onset of illness. Particularly, all household contacts, all daycare/nursery school contacts (children and adults), and healthcare workers who had intimate exposure to secretions (mouth-to-mouth resuscitation, secretions that came in contact with the health-care worker’s mucous membranes) should receive prophylaxis. Family members of the index case have a 400-800 times higher risk of invasive disease. If the index patient only received penicillin for therapy, then the patient should also be treated with chemoprophylaxis to eradicate the organism. School age classmates do not need chemoprophylaxis because they are not at an increased risk of disease. The drug of choice for chemoprophylaxis is rifampin. Ceftriaxone (intravenous or intramuscular) or a single-dose of ciprofloxacin are reasonable alternatives, although resistance to ciprofloxacin has been reported. Azithromycin has also been reported to be effective and can be used in areas with reported ciprofloxacin resistance. All cases require reporting to the local public health department.
A polysaccharide vaccine effective against serogroups A, C, Y, and W-135 was developed in the 1970s. More recently, a conjugate meningococcal vaccine against these four serotypes has been developed. Although the vaccine has been approved for individuals 9 months to 55 years of age, vaccination is recommended for routine administration in adolescents. Early administration is recommended for high-risk groups, including children who are functionally or anatomically asplenic or in those who have terminal complement deficiencies.
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