What antihypertensive medication is recommended for a patient with DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome who is experiencing hypertension due to corticosteroid therapy?

Antihypertensives in DRESS Syndrome

For a patient with DRESS syndrome experiencing corticosteroid-induced hypertension, calcium channel blockers (specifically amlodipine or nifedipine) are the recommended first-line antihypertensive agents, as they are safe, effective, and do not interfere with the immunosuppressive management required for DRESS. 1, 2

Primary Management Considerations

The cornerstone of DRESS syndrome management is immediate discontinuation of the causative drug and initiation of systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day), with a prolonged taper over at least 4 weeks required due to the T-cell immune-directed toxicity mechanism. 1, 3, 4 This extended corticosteroid therapy frequently causes hypertension as a secondary complication, necessitating antihypertensive treatment. 1

Recommended Antihypertensive Algorithm

First-Line: Calcium Channel Blockers

Amlodipine is the preferred agent with the following dosing:

• Start at 5 mg once daily for most patients 2
• May start at 2.5 mg once daily in elderly or hepatically impaired patients 2
• Titrate to maximum 10 mg once daily as needed for blood pressure control 2
• Target blood pressure <130/80 mmHg 1

Amlodipine has Class I, Level A evidence for hypertension management and can be safely used in patients requiring systemic corticosteroids. 1 The 2024 ESC guidelines specifically recommend dihydropyridine CCBs as first-line therapy for blood pressure lowering. 1

Alternative: Nifedipine is also acceptable, particularly for acute severe hypertension, as the 2024 ESC guidelines recommend oral nifedipine for severe hypertension management. 1

Second-Line: Hydralazine

If blood pressure remains uncontrolled on a calcium channel blocker alone, hydralazine should be added as it has Class I, Level A recommendation for persistent hypertension. 1, 5 The 2024 ESC guidelines specifically recommend IV hydralazine as a second-line option for severe hypertension. 1

Third-Line: ACE Inhibitors or ARBs

Once the patient is stabilized on corticosteroids and if additional blood pressure control is needed, consider adding an ACE inhibitor (such as lisinopril) or ARB. 1 These agents have Class I, Level A recommendations for hypertension management and provide cardiovascular mortality benefit. 1

Critical Medications to AVOID

Absolutely Contraindicated

Moxonidine is explicitly contraindicated (Class III, Level B evidence) due to increased mortality risk in similar patient populations. 1, 5 By extension, clonidine should also be avoided despite being an effective antihypertensive, as it shares similar mechanisms and safety concerns. 5

Alpha-adrenoceptor antagonists are NOT recommended (Class III, Level A evidence) due to safety concerns including neurohumoral activation, fluid retention, and worsening clinical status. 1

Use With Extreme Caution

NSAIDs should be avoided when possible, as systemic corticosteroids already cause sodium and water retention, and NSAIDs would compound this effect. 1 The ACC/AHA guidelines recommend considering alternative analgesics such as acetaminophen or tramadol instead. 1

Special Considerations in DRESS Syndrome

Monitoring Requirements

• Monitor blood pressure closely during corticosteroid taper, as hypertension may improve as steroid dose decreases 1
• Assess for fluid retention and electrolyte abnormalities, particularly with corticosteroid therapy 1
• Watch for signs of organ involvement (hepatitis, nephritis, myocarditis) that may influence antihypertensive choice 3, 4

Duration of Therapy

The antihypertensive regimen may need adjustment as corticosteroids are tapered over the required minimum 4-week period. 1, 3, 4 Some patients may be able to discontinue or reduce antihypertensive therapy once corticosteroids are fully tapered, while others with pre-existing hypertension will require ongoing treatment. 1

Renal and Hepatic Considerations

Given that DRESS syndrome frequently involves hepatic (most common organ manifestation) and renal complications, medication dosing must be adjusted accordingly. 3, 4, 6, 7 Amlodipine should be started at 2.5 mg daily in patients with hepatic insufficiency. 2

Common Pitfalls to Avoid

• Do not use negatively inotropic calcium channel blockers (diltiazem or verapamil) if there is any concern for cardiac involvement, as DRESS can cause myocarditis and pericarditis. 1, 3, 4
• Do not prematurely taper corticosteroids to reduce hypertension, as inadequate immunosuppression can lead to DRESS relapse (occurs in approximately 12% of cases). 3, 4
• Do not combine two RAS blockers (ACE inhibitor plus ARB), as this is explicitly not recommended. 1
• Do not use thiazide diuretics as first-line therapy in the acute DRESS setting, as fluid and electrolyte balance is already compromised and requires careful management. 1