A 14-month-old boy with a history of trisomy 21 (Down syndrome), ventricular septal defect repair, and G-tube status post-removal presented to the emergency department from his pediatrician's office with a 24-hour history of fever to 103°F. He had been previously vaccinated, and had a one-day history of rash and nonbloody emesis and diarrhea and rash, which started on his face six hours prior to arrival. In the ED, he is listless, febrile, hypotensive, and tachycardic, and he has a diffuse petechial rash.
What is the diagnosis, and how would you manage this patient in the ED?
Meningococcemia is caused by the encapsulated gram-negative diplococci Neisseria meningitidis that can be acquired by respiratory droplets from an infected host or asymptomatic colonization of the nasopharynx. Up to five percent of people become carriers, with most remaining asymptomatic throughout their lifetimes. Kissing, attending discos and bars, and cigarette smoking have been shown to be independent risk factors for becoming a carrier. (Emerg Infect Dis 2006;12:950.)
This organism is responsible for a variety of disease manifestations including septicemia (meningococcemia), meningitis (most common cause in American children and adults is bacterial meningitis), and septic shock.
Approximately 1.1 per 100,000 people is infected with meningococcus each year in the United States, with nearly 40 percent occurring in children under 2. (J Infect Dis 1999; 180:1894.) Infections are noted to be more common in the winter and early spring, in blacks, and in socioeconomically disadvantaged individuals. Epidemics are unusual in the United States, but do occur in parts of developing countries such as Africa (sub-Saharan African meningitis belt), Asia, and South America. The serogroups A, B, and C are the most common isolates in cases worldwide, with B and C being most prevalent in North America. These serogroups are classified according to their polysaccharide capsule.
Despite the multitude of potential disease manifestations, meningococcemia is one of the most virulent but not the most common. Less than 30 percent of cases of infection with N. meningitidis are isolated bacteremia without meningitis (meningococcemia), with most cases being isolated meningitis. (Pediatrics 2006; 118:e979.) Very rapid disease progression is a hallmark of meningococcemia, often within eight to 24 hours from symptom onset. The initial clinical symptoms can range from an influenza-like prodrome to fulminate illness, including confusion and septic shock. Often the first classic clinical sign on presentation is a petechial (>50%) or hemorrhagic (purpuric) rash due to local vasculitis and thrombocytopenia that commonly develops in areas under pressure such as under the waistband. Septic shock is common, and thought to develop from an intensive inflammatory response to the bacteria's potent lipo-oligosaccharide endotoxin, which quickly leads to vascular collapse.
The differential diagnosis of rash, fever, arthralgias with or without shock should include Rocky Mountain spotted fever, dengue fever, streptococcal infections, influenza, gonococcal infections, thrombotic thrombocytopenic purpura, and other infectious vasculidities.
The diagnosis is made by confirming the presence of N. meningitidis bacteria in sterile body fluid. If the diagnosis is seriously considered, the administration of antibiotics should not be delayed. Studies have shown, however, that in patients with confirmed N. meningitis, cerebrospinal fluid can become culture negative as quickly as 15 minutes after antibiotic administration. (Pediatrics 2001;108:1169.) As such, sterile body fluid should be obtained as quickly as possible after antibiotic administration and sent for culture. Skin biopsy of petechial lesions also may be a source of identification, but has a much lower sensitivity and specificity for detection (approximately 50%). Gram staining should be performed on spinal fluid, joint fluid, and skin biopsy specimens. Other laboratory tests, including a complete blood count with differential and clotting studies (PT, PTT), are also helpful, especially if a coagulopathy is suspected.
Meningococcal infection without treatment is typically fatal (70–90% cases), but mortality rates have improved, and are currently reported to be 10 to 14 percent on average but as high as 40 to 70 percent in fulminant infection since the advent of antibiotics. The risk of death is reported higher in young children. Third-generation cephalosporins are currently the antibiotics of choice for empiric treatment of suspected meningococcal disease with appropriate tailoring based on culture sensitivity results. Treatment of septic shock should follow standard sepsis resuscitation protocols. Early administration of antibiotics when the initial diagnosis of meningococcemia is suspected is thought to decrease mortality significantly. (JAMA 1997;278:491.) These patients should be admitted to the intensive care unit, and an infectious disease specialist should be consulted.
Post-exposure prophylaxis is recommended as soon as possible after a confirmed case of meningococcal disease in all household or close contacts or those with direct contact to saliva or respiratory secretions. Droplet precautions should be maintained for at least 24 hours after the source patient has been treated with antibiotics.
Many possible complications of meningococcemia exist, including arthritis, cranial nerve palsy, pleurisy (all thought to be immunocomplex-mediated), disseminated intravascular coagulopathy (life-threatening condition that becomes obvious with bleeding from gingiva and venipuncture sites), endocarditis, pericarditis, and myocarditis (can lead to myocardial suppression and heart failure), purpura fulminans (characterized by painful ecchymotic papules that progress to hemorrhagic bulla and local gangrenous necrosi,s which can require amputation), Waterhouse-Friderichsen syndrome (adrenal infarction leading to adrenal insufficiency), and death.
In 2005, a quadrivalent conjugate meningococcal vaccine became available in the United States. According to the Centers for Disease Control and Prevention, routine vaccination against meningococcal disease is currently recommended in adolescents 11 to 18 or those 2 to 55 who live in or travel to endemic areas (including sub-Saharan Africa). Revaccination should occur for those children who are considered high risk for infection.
This patient was intubated, appropriately resuscitated, given empiric antibiotics after pan-cultures were collected, and admitted to the pediatric intensive care unit. Blood cultures from the ED were positive for N. meningitidis, serotype B. He was diagnosed with septic shock secondary to meningococcemia, and survived to discharge.
Thanks to Drs. Indi Trehan and Matt Treaster for help in acquiring the photographs and case information.