What is the best course of action for a patient with Behcet's disease, currently on Imuran (azathioprine) 150mg daily and prednisone 5mg, who has been tapering down from 60mg of prednisone over the past 10 months, and is now showing signs of a potential disease flare?

Management of Behçet's Disease on Azathioprine 150mg and Prednisone 5mg with Potential Flare

Continue the prednisone taper by reducing 1mg every 4 weeks until complete discontinuation while maintaining azathioprine 150mg daily, with monthly monitoring for disease activity during the taper. 1

Rationale for Continuing the Taper

Your patient has successfully tapered from 60mg to 5mg prednisone over 10 months, demonstrating disease stability on the current regimen. The goal should be azathioprine monotherapy to avoid long-term corticosteroid complications. 1, 2

• Azathioprine monotherapy is highly effective for maintenance: 87% of patients with autoimmune conditions remain in remission during observation periods up to 67 months after prednisone withdrawal when maintained on azathioprine at approximately 2 mg/kg/day. 1, 2

• Your patient's azathioprine dose is appropriate: 150mg daily represents approximately 2 mg/kg for most adults, which is the optimal maintenance dose. 1

• The primary advantage is avoiding corticosteroid toxicity: Given 10 months of exposure already, eliminating prednisone prevents further bone loss, metabolic complications, and other steroid-related morbidity. 1, 2

Specific Tapering Protocol

Reduce prednisone by 1mg every 4 weeks until complete discontinuation. 1

• Do NOT taper faster: Reductions of 5mg weekly lead to disease flare or symptomatic adrenal insufficiency. 1

• Maintain azathioprine at 150mg daily throughout the entire taper without any dose changes. 1

• Provide stress-dosing education: The patient needs instructions for supplemental corticosteroids during acute illness or physiologic stress while tapering and for 12 months after discontinuation. 1

Monthly Monitoring Requirements During Taper

Clinical assessment at each monthly visit must include: 1, 2

• Mucocutaneous manifestations: Oral ulcers, genital ulcers, skin lesions (erythema nodosum, pseudofolliculitis)
• Ocular symptoms: Vision changes, eye pain, photophobia, floaters (critical as ocular involvement predicts worse outcomes)
• Joint symptoms: Arthralgia or arthritis
• Systemic manifestations: Vascular symptoms, neurologic symptoms, gastrointestinal symptoms

Laboratory monitoring every month during taper: 2, 3

• Complete blood count: Azathioprine causes lymphopenia in 57% of patients and myelosuppression in 7%, making this non-negotiable. 2, 3
• Liver function tests: Monitor for hepatotoxicity
• Renal function: Baseline monitoring

Managing a Disease Flare During Taper

If Behçet's symptoms recur at any point during the taper: 1

1. Immediately return to the pre-relapse prednisone dose (the dose before symptoms appeared)
2. Maintain that dose for 4-8 weeks until symptoms resolve
3. Verify azathioprine compliance by checking pharmacy records and looking for macrocytosis on CBC as a compliance marker 2
4. Resume tapering more slowly once disease activity is controlled

If a significant flare occurs (severe ocular involvement, CNS involvement, major organ involvement): 4

• Treatment may require steroid doses similar to the original induction regimen (up to 60mg prednisone daily or pulse methylprednisolone 500-750mg IV for 3 consecutive days). 4
• Earlier detection of relapse allows lower doses of immunosuppressants to re-induce remission. 4
• Patients who flare during adequate maintenance therapy should be kept on immunosuppression permanently. 4

Critical Monitoring for Azathioprine Toxicity

Hematologic surveillance is mandatory: 2, 3

• Lymphopenia occurs in 57% of patients on azathioprine—this is expected but requires monitoring. 2
• Dose reduction is required if: Lymphocyte count <0.5 × 10⁹/L, platelet count <50 × 10⁹/L, or neutrophil count <1.0 × 10⁹/L. 3
• Check TPMT status if not already done: TPMT deficiency increases risk of life-threatening myelosuppression. 2, 3

Drug Interaction Warning

If the patient requires allopurinol or other xanthine oxidase inhibitors: 2

• Azathioprine dose must be reduced to 25-33% of the usual dose (approximately 40-50mg daily) due to severe myelosuppression risk. 2
• This interaction is life-threatening if not recognized.

Expected Outcome

Most patients successfully discontinue prednisone when azathioprine is properly dosed and disease has been stable. 1

• The combination of azathioprine with low-dose prednisone is well-tolerated long-term, with 87% of patients successfully managed on ≤10mg prednisone daily for observation periods up to 149 months. 2
• Side effects from earlier high-dose corticosteroid treatment improve or disappear in 85% of patients once prednisone is reduced or discontinued. 2

Common Pitfalls to Avoid

• Tapering too quickly: This is the most common error leading to flare or adrenal insufficiency. 1
• Assuming compliance without verification: Always check pharmacy records and review CBC for macrocytosis as a compliance marker. 2
• Failing to educate about stress dosing: Patients need clear instructions for supplemental steroids during illness. 1
• Inadequate monitoring frequency: Monthly visits are essential during the taper to detect early flare. 1