z
WATERHOUSE
FRIEDERICKSEN
SYNDROME.
Harry Jim Esther
group 566
z

DEFINITION


Waterhouse-Friderichsen syndrome (WFS) or hemorrhagic
adrenalitis or Fulminant meningococcemia, is defined as adrenal
gland failure due to bleeding into the adrenal glands, caused by
severe bacterial infection (most commonly the meningococcus
Neisseria meningitidis).


Another definition is; acute and severe meningococcemia with
hemorrhage into the adrenal glands
ETIOLOGY
z
1. Most common causes
Group B streptococcus
Pseudomonas aeruginosa
S. pneumoniae
Staphylococcus aureus
2. Rarely, Waterhouse-Friderichsen syndrome can be caused
by the use of medications that promote blood clotting.
3. Other causes include
Low platelet counts
Primary antiphospholipid syndrome
Renal vein thrombosis
Steroid use
z
Occur usually in infants or children younger than 10,
occasionally in adults.
The Waterhouse-Friderichsen syndrome may develop in 10 to
20 percent of children with meningococcal infection.
This syndrome is characterized by:
✓ Large petechial hemorrhages in the skin and mucous
membranes
✓ Fever
✓ Septic Shock
✓ Disseminated Intravascular Coagulation
z

CLINICAL PICTURE

Onset of the syndrome is dramatically sudden. Nonspecific with fever (initially
moderate, then high), rigors, cough, vomiting, and headache. Dysphagia,
atrophy of of the tongue, and cracks at the corners of the mouth are also
characteristic features.

Soon a rash appears; first macular, not much different from om the rose spots
of typhoid, and rapidly becoming petechial and purpuric with a dusky gray
color and sometimes large purpuric cutaneous haemorrhages often followed
by necrosis and sloughing.

Exhibits a cyanotic pallor, patients are alert but pale with coldness and
cyanosis of the extremities due to generalized vasoconstriction.

Hypotension and rapidly leads to septic shock.
z

COMPLICATION

Shock, extensive haemorrhage within the skin and fall into
coma.

Death usually after a few hours, adrenal insufficiency being
the immediate cause.

Patients who recover may suffer from extensive sloughing
of the skin and loss of digits due to gangrene.

MENINGITIS GENERALLY DOES NOT OCCUR.

z
DIAGNOSTIC METHOD
There is hypoglycemia with hyponatremia and
hyperkalemia, and the ACTH stimulation test demonstrates
the acute adrenal failure.

Leukocytosis but if leukopenia is seen, it became a very
poor prognostic sign.

C-reactive protein levels can be elevated or almost normal.

Thrombocytopenia With alteration in and partial
thromboplastin prothrombin time time (PTT) suggestive of
diffuse intravascular coagulation (DIC).

Acidosis and acute renal failure can be seen as in any
severe sepsis.

Meningococci can be readily cultured from blood or CSF or
smears of cutaneous lesions.
z

PREVENTION

Routine vaccination against meningococcus is recommended by
the Centers for Disease Control for;

All 11-18 year olds

2 People who have poor splenic function (who, for example, have
had their spleen removed or who have sickle-cell disease which
damages the spleen)

3. Who have certain immune disorders, such as a complement
deficiency.
z
 TREATMENT

The treatment is as that for meningococcal infection, fulminant
meningococcemia is a medical emergency and needs to be
treated with adequate antibiotics as fast as possible.

Ceftriaxone is an antibiotic commonly employed today.
Ceftriaxone is a third-generation cephalosporin antibiotic. Like
other third- generation cephalosporins, it has broad spectrum
activity against Gram-positive and Gram-negative bacteria. In
most cases, it is considered to be equivalent to cefotaxime in
terms of safety and efficacy.

Benzylpenicillin was once the drug of choice with
chloramphenicol as a good alternative in allergic patients.
z
 Addition of adrenal support with hydrocortisone, given
intravenously in a dose of 200 mg per square metre
body surface per four hours. Hydrocortisone can
sometimes reverse the hypoadrenal shock.
 Hypovolaemia is treated with colloids, dopamine and
coagulation factors.
 Sometimes plastic surgery and grafting is needed to
deal with tissue necrosis.
z

Case 1

A 4 year old, previously healthy boy has a short history of cough and
malaise, which had also affected other family members. On attending
the accident and emergency department he was found to have a fever
of 39°C, an erythematous, blanching skin rash, mild pharyngitis, and
cervical lymphadenopathy. A diagnosis of viral infection was made and
he was sent home. Five days later his condition worsened, with shock
and a confluent haemorrhagic rash. His temperature remained high
and he was noted to be tachypnoeic. Clotting parameters, including D
dimers, were abnormal and his platelet count was low, consistent with
disseminated intravascular coagulation. Despite resuscitation, he died.
 At necropsy there were signs of upper airway infection and
z
bilateral basal bronchopneumonia, with consolidation. Massive
haemorrhage was present in the right adrenal gland, but not the
left. There was no evidence of meningitis or haemorrhage
elsewhere. Microvascular thrombi were not seen on histology.

The cause of death was given as acute adrenal haemorrhage as
a result of meningococcal septicaemia. Family members were
given antibiotic prophylaxis and the consultant in communicable
diseases was informed. Blood cultures and skin scrapings taken
before death were unhelpful. Blood and pleural fluid taken
aseptically at necropsy grew a heavy pure growth of ẞ
haemolytic streptococcus group A. Other surface swabs also
grew streptococcus group A. The isolates typed as the M1 strain
and contained genes for toxins A and B (the cause of
streptococcal toxic shock syndrome). Polymerase chain reaction
for meningococcal DNA was negative.
z

Case 2

Case 2 was a 64 year old man who died suddenly and
unexpectedly at home, with no known preceding illness. He had
undergone a laparotomy following abdominal trauma at age 14
years, with splenectomy, and had a history of rheumatoid arthritis
treated with methotrexate.

At necropsy a skin rash was noted. The lungs were congested and
massive bilateral adrenal haemorrhages were present (fig 1). The
spleen was absent and the upper peritoneum was studded with
multiple soft splenunculi. The brain showed severe vascular
congestion within the choroid plexus, with mild cerebral oedema.
There was no evidence of meningitis or haemorrhage elsewhere
and microvascular thrombi were not seen on histology.

Postmortem blood cultures, taken aseptically, grew a pure growth of
S pneumoniae.
z
Figure 1 Postmortem histology from case 2 showing massive adrenal haemorrhage, low power
and (inset) high power. Haematoxylin and eosin stain.
z