MENINGOCOCCEMIA
Meningococcemia can cause a wide range of clinical diseases, of which neisserial meningitis is the most severe and life-threatening. The bacteria, Neisseria meningitidis, is capable of causing septicemia, pneumonia, and meningitis. These are all relentless diseases that are universally fatal if not promptly treated. The bacteria has been known to cause severe disseminated intravascular coagulation (DIC) and the Waterhouse-Friderichsen syndrome. The latter syndrome, also known as acute adrenocortical insufficiency, is directly caused by hemorrhagic destruction of both adrenal glands. This syndrome can result from a wide range of conditions, including infections, and N. meningitidis is one of the more frequent infectious causes.
Clinical
Findings: Children younger than 1 year of age are those most likely to develop
disease from N. meningitidis infection. Boys are more
apt to develop this infection than girls, and there is no race predilection.
One risk factor appears to be the presence of a smoker in the household. It is
theorized that the secondhand smoke damages the child’s respiratory epithelium
just enough to allow the bacteria to penetrate the mucous membranes and enter
the bloodstream. Other risk factors include a deficiency of the complement
components C5, C6, C7, and C8. Asplenia also increases one’s risk, because the
spleen is extremely important in removing encapsulated bacteria from the
bloodstream. Chronic immunosuppression increases the risk, as does living in
crowded conditions. This is why military barracks and college dormitories are
often sources of outbreaks.
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| Plate 6-19 ACUTE ADRENAL INSUFFICIENCY (WATERHOUSE-FRIDERICHSEN SYNDROME) |
Patients who
develop meningitis have fever, head- ache, vomiting, stiff neck, and meningeal
physical signs, including Kernig’s sign and Brudzinski’s sign. Kernig’s sign is
positive when placing a patient’s hips and knees in 90-degree flexion and
extending the knee joint elicits pain. Brudzinski’s sign is more sensitive for
meningitis and is positive when flexing of the patient’s neck causes flexion of
the hips and knees. These signs have long been used to help diagnosis
meningitis clinically. As the disease progresses, seizures or coma may occur.
Cutaneous
findings include palpable purpura, ecchymosis, widespread macular purpura, and
necrosis of the skin with secondary vesiculopustules. The purpura can be
angulated with an irregular border. Centrally within the purpuric region, there
is often a dusky gray discoloration of the skin. Patients often complain of
skin pain. Necrosis may progress to cause gangrene of the digits or distal
extremities. In severe cases, entire limbs can become gangrenous. If DIC sets
in, the clinical skin findings of DIC may be seen on top of the initial skin
findings. The presence of DIC is a poor prognostic indicator.
Fulminant
meningococcal septicemia may lead to hemorrhagic necrosis of the adrenal
glands; this is termed the Waterhouse-Friderichsen syndrome. It leads
ultimately to acute adrenal dysfunction. This syndrome is seen in fewer than 5% of patients with
N.
meningitidis septicemia, but it occurs in more than 50% of the fatal cases. Patients
present with skin findings of widespread purpura and cyanosis. They have signs
and symptoms of hemodynamic collapse, hypotension, acute renal failure, and a
biphasic fever. The skin findings are caused by small-vessel embolization or
endothelial destruction from the septicemia. Blood extravasates through the
damaged endothelial walls and produces massive purpura. The more extensive the
cutaneous purpura in meningococcal septicemia, the higher the incidence of
Waterhouse-Friderichsen syndrome.
Laboratory
testing can be used to diagnosis the disease, but one should not wait for the
results to begin therapy if there is a high clinical suspicion of N. meningitidis infection. Culture of N.
meningitidis from blood, cerebral spinal fluid (CSF), or tissue is
diagnostic. The gram-negative diplococcal bacteria grows on the chocolate agar
plate and appears as small, round, moist, gray colonies. Gram staining of CSF
shows intracellular gram-negative diplococcal bacteria. This bacteria also
grows well on the Thayer-Martin agar plate. The bacteria is oxidase positive
and is able to acidify certain sugars. These laboratory data can be used to
help differentiate N. meningitidis from other bacteria. CSF samples can
be used for polymerase chain reaction (PCR) testing for the bacteria, but this
is not routinely done in these cases. All cases of N. meningitidis infection
should be reported to state and national health organizations.
Pathogenesis:
Meningococcal
infections, including septicemia and meningitis, are caused by the gram-
negative bacteria, N. meningitidis. This is a diplococcal bacterium that
requires an iron source for survival. Because of this unique metabolic
requirement, humans are the only known host. The meningococcus bacteria can be
found as a transient colonizer in the oropharynx of up to 10% of sampled
individuals. These carriers express no sequelae but serve as a potential
reservoir for meningococcal disease. The organisms are spread by close contact
and sharing of saliva. If the bacteria is able to reproduce to such an extent
as to cause bacteremia, it then becomes a potential pathogen. Bacteremia can
quickly lead to septicemia (meningococcemia). This is a severe,
life-threatening disease that can kill quickly. Meningeal involvement leads to
neisserial meningitis. The bacteria exhibit a neurotrophic behavior and attack
the lining of the central nervous system.
At least 13
serotypes of N. meningitidis are known, 9 of which have been conclusively shown to cause human
disease. Currently, a vaccine is available that protects against the serotypes
that most frequently cause disease: serotypes A, C, Y, and W-135. The remaining
five serotypes can affect any individual regardless of vaccination status. The
bacteria expresses a
toxin (lipooligosaccharide) on its surface that causes many of the systemic
symptoms of disease. N. meningitidis is an encapsulated bacteria, and
this helps protect it from the host’s immune system.
Histology:
Most
skin biopsy specimens show evidence of vasculitis with neutrophils, fibrinoid
necrosis, and extravasated red blood cells. Organisms can be appreciated on
tissue Gram stains. Embolism of capillaries and small venules is often seen,
and necrosis and ulceration can be secondary findings.
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| Plate 6-20 BACTERIAL MENINGITIS |
Treatment:
Treatment
requires prompt recognition of symptoms and immediate intravenous antibiotic
therapy. Any close contacts of the patient should be screened for evidence of
disease and given prophylactic oral therapy to decrease the potential of an
epidemic. The main intravenous antibiotic of choice is ceftriaxone, followed by
penicillin or by chloramphenicol in penicillin-allergic patients. Patients with
Waterhouse-Friderichsen syndrome need adrenal gland replacement therapy.
Contacts
should be treated with ciprofloxacin, rifampin, or ceftriaxone. This
prophylactic therapy, as well as intravenous therapy, should be started
immediately if clinical suspicion is high enough; delaying therapy for even a
few hours to wait for laboratory confirmation can be the difference between life and death.
Immunization
is helping to keep the disease incidence low, and guidelines have been
established for which high-risk groups should get the vaccine and when.
Although the vaccine protects against only 4 of the 13 serotypes of N. meningitidis,
it has the potential to decrease the incidence of this disease and save many lives.
