How should a patient with a history of adrenal insufficiency be managed when diagnosed with vasculitis?

Management of Vasculitis in Patients with Pre-existing Adrenal Insufficiency

Patients with pre-existing adrenal insufficiency who develop vasculitis require immediate stress-dose glucocorticoid coverage (hydrocortisone 100 mg IV bolus followed by 100-300 mg/day continuous infusion) while simultaneously initiating aggressive vasculitis treatment with high-dose glucocorticoids plus either cyclophosphamide or rituximab. 1

Immediate Management Algorithm

Step 1: Prevent Adrenal Crisis

• Administer hydrocortisone 100 mg IV bolus immediately upon diagnosis of vasculitis 1
• Follow with continuous infusion of 100-300 mg/day hydrocortisone OR divided doses every 6 hours 1
• The high-dose hydrocortisone (100 mg) saturates mineralocorticoid receptors, eliminating the need for separate fludrocortisone during acute crisis 1
• Provide rapid IV fluid resuscitation with 3-4 L isotonic saline or 5% dextrose in isotonic saline at approximately 1 L/hour initially 1

Step 2: Initiate Vasculitis Treatment

For organ-threatening or life-threatening vasculitis (which includes most ANCA-associated vasculitis presentations):

• Start remission-induction therapy with glucocorticoids PLUS either cyclophosphamide OR rituximab 1
• Rituximab is preferred over cyclophosphamide in relapsing disease, women of childbearing age, or when fertility preservation is important 1
• Standard rituximab dosing: 375 mg/m² IV weekly for 4 weeks 1

Step 3: Glucocorticoid Dosing Strategy

Critical distinction: Your patient needs TWO separate glucocorticoid considerations:

1. Stress-dose coverage for adrenal insufficiency (hydrocortisone 100-300 mg/day IV initially) 1
2. Immunosuppressive therapy for vasculitis (prednisolone 1 mg/kg/day, max 60 mg) 1, 2

The stress-dose hydrocortisone provides both adrenal replacement AND initial immunosuppression. Once the patient stabilizes (typically 3-7 days), transition to:

• Oral prednisolone 1 mg/kg/day (maximum 60 mg/day) for vasculitis treatment 1, 2
• PLUS maintenance hydrocortisone 10-20 mg in morning, 5-10 mg early afternoon for baseline adrenal insufficiency 3
• Add fludrocortisone 0.1 mg/day if primary adrenal insufficiency (not needed if secondary) 3

Glucocorticoid Tapering Protocol

Month 1: Maintain prednisolone at 1 mg/kg/day (max 60 mg) 1

Months 2-3: Taper to target dose of 10-15 mg/day by 3 months 1

Critical pitfall: Do NOT use alternate-day therapy—this increases relapse risk 1

After achieving remission: Continue tapering prednisolone toward the patient's baseline maintenance dose for adrenal insufficiency (typically 5-10 mg prednisone equivalent daily) 3

Maintenance Therapy Selection

After remission induction (typically 3-6 months):

• Rituximab 500 mg IV every 6 months is superior to azathioprine and is the preferred maintenance agent 1
• Alternative options: azathioprine, methotrexate, or mycophenolate mofetil 3, 1
• Continue maintenance therapy for at least 18-24 months following sustained remission 1

Critical Monitoring Requirements

Clinical Assessment (NOT ANCA levels)

• Use structured clinical assessment rather than ANCA testing to guide treatment changes 3, 1
• Monitor four-extremity blood pressures and perform complete vascular examination at each visit 4
• Assess for signs of adrenal crisis: hypotension, hyponatremia, hyperkalemia, hypoglycemia 3, 5

Laboratory Monitoring

• Check serum immunoglobulin levels before each rituximab course and with recurrent infections 3, 1
• Monitor for cyclophosphamide-related bladder toxicity with urinalysis 3
• Assess cardiovascular risk periodically 3, 1

Imaging Follow-up

• Schedule cross-sectional imaging every 3-6 months during active disease 4

Special Considerations and Pitfalls

Refractory Disease

If inadequate response after 4 weeks OR <50% reduction in disease activity at 6 weeks:

• Switch from cyclophosphamide to rituximab or vice versa 1
• Manage in conjunction with expert vasculitis center 3

Severe Renal Involvement

Consider plasma exchange for:

• Serum creatinine >3.4 mg/dL (>300 μmol/L) 1
• Patients requiring dialysis 1
• Rapidly increasing creatinine 1

Bone Protection

• Implement bone protection therapy according to local guidelines for ALL patients on glucocorticoids 1
• This is especially critical given the dual glucocorticoid burden (vasculitis treatment + adrenal replacement) 2

Patient Education Essentials

• Provide medical alert bracelet indicating both adrenal insufficiency AND vasculitis 3
• Train patient and family in emergency intramuscular hydrocortisone administration 3
• Educate on stress-dosing: double or triple maintenance glucocorticoids during illness, injury, or procedures 3
• Ensure endocrine consultation before any surgery for stress-dose planning 3

Long-term Adrenal Function

Important caveat: High-dose glucocorticoid therapy for vasculitis will suppress the hypothalamic-pituitary-adrenal axis, potentially causing iatrogenic secondary adrenal insufficiency that persists after vasculitis treatment ends 3, 6. In one study of giant cell arteritis patients, mean time to adrenal recovery was 14 months (range up to 51 months), and 5% never recovered 6. Perform ACTH stimulation testing when tapering below 5 mg prednisolone daily to assess recovery 3, 6.