What is the best course of treatment for a patient presenting with adrenal congestion and a purpuric rash, potentially indicating Waterhouse-Friderichsen syndrome?

Waterhouse-Friderichsen Syndrome: Emergency Management

Immediate IV hydrocortisone 100 mg bolus plus aggressive fluid resuscitation with 0.9% saline at 1 L/hour must be initiated without delay—treatment should NEVER be postponed for diagnostic confirmation when adrenal congestion with purpuric rash suggests Waterhouse-Friderichsen syndrome. 1

Immediate Life-Saving Interventions

Administer within minutes of recognition:

• IV hydrocortisone 100 mg bolus immediately, followed by 100 mg every 6-8 hours 1, 2
• 0.9% saline infusion at 1 L/hour (minimum 2L total) to reverse shock 1, 3
• Broad-spectrum antibiotics (ceftriaxone 2g IV is preferred for suspected meningococcal disease) 1, 4, 5
• Target lactate normalization and urine output ≥0.5 mL/kg/h as endpoints of resuscitation 1

The UK Joint Specialist Societies explicitly state that although Waterhouse-Friderichsen syndrome with adrenal failure is rare, low-dose steroid supplementation may improve survival in refractory septic shock with documented adrenal hypo-responsiveness 1. In pediatric septic shock with purpura fulminans, approximately 25% have absolute adrenal insufficiency, and death can occur within 8 hours without hydrocortisone 1.

Critical Diagnostic Clues

Recognize this constellation immediately:

• Rapidly progressing purpuric or petechial rash (present in 89% of meningococcal cases with rash) 1
• Hypotension and shock despite fluid resuscitation 1
• Lactate >4 mmol/L indicating cryptic shock 1
• Hyponatremia (present in 90% of adrenal insufficiency cases) 6, 7, 3
• Coagulopathy with low platelets, low fibrinogen, elevated clotting times indicating DIC 1, 8

Common pitfall: Do not wait for hyperkalemia—it occurs in only ~50% of acute adrenal insufficiency cases and may be absent in Waterhouse-Friderichsen syndrome 6, 7, 3. The absence of hyperkalemia cannot rule out adrenal failure 6.

Pathophysiology-Driven Management

Waterhouse-Friderichsen syndrome results from bilateral adrenal hemorrhagic necrosis, most commonly from Neisseria meningitidis but also reported with Streptococcus pneumoniae, Staphylococcus aureus, and rarely Proteus mirabilis 4, 5, 9, 8, 10. The shock mechanism involves:

• Hypovolemia from capillary leak syndrome 1
• Myocardial dysfunction 1
• Altered vasomotor tone 1
• Acute adrenal insufficiency from hemorrhagic destruction 1

Patients are often deficient in protein C, protein S, and antithrombin III with defective endothelial protein C activation 1. This drives the purpura fulminans and DIC.

Adjunctive Critical Care Measures

Blood product support:

• Treat overt DIC with platelets, fresh frozen plasma, and cryoprecipitate per established DIC guidelines 1
• Correct anemia, thrombocytopenia, and coagulopathy in consultation with hematology 1
• Consider plasma infusion to replace protein C, antithrombin III, and ADAMTS13 in progressive purpura with thrombocytopenia-associated multiple organ failure 1

Vasopressor therapy:

• Albumin should be considered in worsening shock requiring significant fluid resuscitation (subgroup analysis showed improved survival in severe sepsis with shock) 1
• Vasopressors are indicated when hypotension persists despite adequate fluid resuscitation 1

Seizure management:

• Seizures occur in 15% of bacterial meningitis and worsen outcomes—start anticonvulsants promptly even when suspected but not proven 1
• EEG monitoring for suspected status epilepticus 1

Hydrocortisone Dosing Specifics

Stress-dose hydrocortisone protocol (from FDA labeling and guidelines):

• Initial dose: 100-500 mg IV depending on severity 2
• In overwhelming, acute, life-threatening situations (which Waterhouse-Friderichsen syndrome qualifies as), doses exceeding usual dosages are justified 2
• Repeat every 2,4, or 6 hours based on clinical response 2
• Pediatric dosing: 50 mg/m²/24h up to 50 mg/kg/day may be required to reverse shock 1

The American College of Critical Care Medicine specifically recommends hydrocortisone for children with fluid-refractory, catecholamine-resistant shock and suspected absolute adrenal insufficiency, particularly those with severe septic shock and purpura 1.

Public Health Notification

Mandatory reporting and prophylaxis:

• Notify public health authority immediately (legal obligation in UK and similar jurisdictions) 1
• Contact Consultant in Communicable Disease Control early 1
• Ciprofloxacin prophylaxis for close contacts: 500 mg stat for adults, 250 mg for children 5-12 years, 30 mg/kg (max 125 mg) for children <5 years 1
• Alternative: Rifampicin 600 mg twice daily for 2 days (adults >12 years) 1

Prognosis and Risk Factors for Fatal Outcome

High-risk features associated with mortality (from UK guidelines):

• Rapidly progressing rash 1
• Coma 1
• Hypotension and shock 1
• Lactate >4 mmol/L 1
• Low/normal peripheral white blood cell count 1
• Low acute phase reactants 1
• Low platelets 1
• Coagulopathy 1
• Absence of meningitis (isolated sepsis worse than meningitis) 1

Case reports document mortality within 24 hours of symptom onset despite intensive treatment 4, 10. The fulminant progression demands immediate recognition and treatment without diagnostic delay 1, 3.