1. Waterhouse–Friderichsen
syndrome (WFS)
By Stacy Arvinna Binti Jamarun
Group 3
6th Year 2nd Semester
Paedriatic Disease

2. 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

3. ETIOLOGY
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. CLINICAL PICTURE
 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.

6. 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.

7. 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
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. PREVENTION
 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. 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.

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.

15. Than
k
you!!