Is an Angiotensin-Converting Enzyme (ACE) inhibitor more likely to cause a skin rash than an Angiotensin Receptor Blocker (ARB)?

ACE Inhibitors Are More Likely to Cause Skin Rash Than Angiotensin Receptor Blockers

ACE inhibitors have a significantly higher incidence of skin reactions, including rash and angioedema, compared to Angiotensin Receptor Blockers (ARBs). 1 This difference is primarily due to their distinct mechanisms of action and effects on bradykinin metabolism.

Mechanism Behind Skin Reactions

ACE Inhibitors

• Block conversion of angiotensin I to angiotensin II
• Inhibit breakdown of bradykinin, leading to accumulation 1
• Bradykinin accumulation is responsible for many skin-related adverse effects 1
• Estimated overall incidence of adverse effects is 28%, with approximately half occurring in the skin 2

Angiotensin Receptor Blockers

• Block angiotensin II receptors directly
• Do not inhibit kininase, resulting in minimal effect on bradykinin levels 1
• Associated with a lower incidence of skin reactions including rash and angioedema 1

Comparative Incidence of Skin Reactions

Angioedema

• ACE inhibitors: Occurs in approximately 0.1% to 0.7% of patients 3
• ARBs: Approximately half the rate of ACE inhibitors (around 0.1%) 4
• Risk factors for ACE inhibitor-induced angioedema include:
  • Black race
  • Female sex
  • History of smoking
  • Increasing age 3
  • History of drug rash
  • Seasonal allergies 4

Cough and Other Skin Reactions

• ACE inhibitors cause cough in up to 20% of patients 1
• Clinical trials comparing losartan (ARB) with lisinopril (ACE inhibitor) showed significantly lower incidence of cough with ARBs 5
• Other skin reactions more common with ACE inhibitors include:
  • Pruritus
  • Bullous eruptions
  • Urticaria
  • Generalized rashes
  • Photosensitivity
  • Hair loss 2

Cross-Reactivity Concerns

• For patients with ACE inhibitor-induced angioedema who switch to ARBs, there is a modest risk (2-17%) of recurrent angioedema 3
• Despite this risk, most patients who experienced ACE inhibitor-induced angioedema can safely use ARBs without recurrence 3
• Some studies suggest caution when using ARBs in patients with a history of angioedema from ACE inhibitors 6, 7

Clinical Implications

• ARBs are recommended as an alternative therapy for patients with a history of ACE inhibitor-induced skin reactions 1
• When switching from an ACE inhibitor to an ARB due to skin reactions, patients should be monitored closely, especially in the first few weeks
• Both medication classes require monitoring of blood pressure, renal function, and potassium levels 1

Important Caveats

• Angioedema from ACE inhibitors may occur at any time during treatment and can continue even after discontinuation 4
• Unlike histamine-mediated reactions, ACE inhibitor-induced angioedema does not reliably respond to treatment with epinephrine, antihistamines, or corticosteroids 3
• Discontinuation of the ACE inhibitor (or ARB) is the cornerstone of therapy for drug-associated angioedema 3

In conclusion, when considering the risk of skin rash and other cutaneous reactions, ARBs have a more favorable side effect profile than ACE inhibitors, making them a better option for patients with a history of skin reactions or those at higher risk for developing such reactions.