Waterhouse-Friderichsen Syndrome

Waterhouse-Friderichsen syndrome is acute bilateral adrenal haemorrhage, with adrenal failure and shock, complicating fulminant bacteraemia, classically meningococcaemia. It is a form of purpura fulminans with adrenal crisis.

Epidemiology. It occurs in a minority of patients with severe meningococcal septicaemia. Other organisms include Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus. Children and young adults are mostly affected, and mortality is very high without early treatment.

Pathophysiology. Endotoxin and DIC cause adrenal vein thrombosis, endothelial injury and haemorrhagic infarction. Loss of cortisol and aldosterone aggravates vasodilation, hypotension, hypoglycaemia, hyponatraemia and hyperkalaemia.

Presentation is fever, rapid onset of widespread purpura, hypotension unresponsive to fluid and vasopressors, tachycardia, confusion, abdominal or flank pain, vomiting, and hypoglycaemia. Meningism may or may not be present.

Red flags.

• Purpuric rash with refractory shock.
• Hypoglycaemia, sodium under 130 mmol/L or potassium over 5.5 mmol/L.
• Rapid progression over hours.

Treat before confirmation. Blood cultures and nucleic acid amplification testing, full blood count, coagulation, fibrinogen, glucose, electrolytes, lactate, creatinine and random cortisol (taken before hydrocortisone if it does not delay treatment). A cortisol under 276 nmol/L (10 microgram/dL) in shock suggests insufficiency. CT shows enlarged or haemorrhagic adrenals when the patient is stable.

Differential diagnosis. Other septic shock, toxic shock syndromes, primary adrenal insufficiency, adrenal haemorrhage from anticoagulants or antiphospholipid syndrome, and DIC.

Antibiotics within 1 hour. Ceftriaxone 2 g IV every 12 hours (children 80 mg/kg daily, maximum 4 g), with benzylpenicillin 1.2 g IV or IM before hospital arrival. Adjust to organism.

Hydrocortisone. 100 mg IV bolus (children 2 to 4 mg/kg, to a maximum of 100 mg), then 200 mg daily by continuous infusion, or 50 mg IV every 6 hours. Do not wait for cortisol results. Doses over 50 mg daily give adequate mineralocorticoid effect, so fludrocortisone is not needed in the acute phase.

Fluids and vasopressors. Crystalloid boluses of 20 mL/kg (500 mL adults) to 40 to 60 mL/kg with reassessment, then noradrenaline or adrenaline 0.05 to 1 microgram/kg/min.

Correct metabolic disorders. Dextrose 25 g IV for hypoglycaemia (2 mL/kg of 10% dextrose in children), treatment of hyperkalaemia, and sodium replacement with 0.9% sodium chloride.

Coagulopathy. Plasma, cryoprecipitate and platelets for bleeding, to the same targets used in purpura fulminans (platelets over 50 x 10^9/L, fibrinogen over 1.5 g/L).

Long term care. Reassess adrenal function after recovery (short corticotropin stimulation test), because adrenal necrosis often leaves permanent failure needing hydrocortisone 15 to 25 mg daily in divided doses and fludrocortisone 50 to 200 microgram daily, with sick day rules and an emergency card.

Public health. Notify and give chemoprophylaxis to close contacts within 24 hours: ciprofloxacin 500 mg orally once (adults), rifampicin 600 mg orally every 12 hours for 2 days, or ceftriaxone 250 mg IM once (pregnancy).

Monitoring. Haemodynamics, glucose hourly, electrolytes every 4 to 6 hours, urine output and coagulation.

Referral and escalation. Intensive care, endocrinology, and infection and public health teams.

Special groups. In pregnancy, use the same treatment. In children, glucose monitoring is vital.