The document describes Waterhouse-Friderichsen syndrome (WFS), which is defined as adrenal gland failure caused by hemorrhaging into the adrenal glands due to severe bacterial infection, most commonly by Neisseria meningitidis bacteria. WFS is characterized by petechial rashes, fever, septic shock, and disseminated intravascular coagulation. It typically affects infants and children under 10 years old. Treatment involves antibiotics, adrenal hormone replacement, and managing shock. Two case studies are presented of patients who died from WFS caused by group A streptococcus and Streptococcus pneumoniae respectively.

1. Habiba Ramon-Yusuf
Group 507

2.  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

3. 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

4.  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

5.  Onset of the syndrome is dramatically sudden.
 Nonspecific with fever (initially moderate, then
high), rigors, cough, vomiting, and headache.
Dysphagia, atrophy 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 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.

6.  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.

7.  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
prothrombin time (PT) and partial thromboplastin
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.

8.  Routine vaccination against meningococcus is
recommended by the Centers for Disease
Control for;
1. 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.

9.  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.

10.  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.

11. 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.

12.  At necropsy there were signs of upper airway
infection and 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 β 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.

13. 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.

14.  Figure 1 Postmortem histology from case 2 showing
massive adrenal haemorrhage, low power and (inset)
high power. Haematoxylin and eosin stain.

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