Buy Micardis through the unique service that maximize your savings

Abstract
A 61-year-old patient who had been treated with lisinopril in the past without any problems was commenced on ramipril for left ventricular dysfunction. He developed a painful symmetrical purpuric eruption over both feet after three days. A full vasculitis screen was negative. Ramipril was stopped and he required a course of steroids after which the rash improved slowly.
The ACE inhibitors can cause various skin side effects; however, it rarely causes cutaneous vasculitis. Ramipril-induced cutaneous vasculitis is particularly rare and our case was atypical because the patient had tolerated lisinopril before. Previous successful treatment with one ACE inhibitor does not rule out the vasculitis caused by the drug from the same group.

Related Results

RAMIPRIL.Sandoz launches ramiprilRamipril cuts diabetes riskRamipril-associated hepatotoxicityRamipril in rheumatoid arthritis

Here we report ramipril-induced cutaneous vasculitis in a patient who required steroid therapy to control it.
**********
Case Report
A 46-year-old gentleman developed a cutaneous vasculitic rash over his feet 3 days after starting ramipril and bisoprolol for left ventricular dysfunction. His medical history included Tetralogy of Fallot, corrected at the age of 14, ankylosing spondylitis, and Marfan’s syndrome. He had previously been on lisinopril for 5 years for reduced left ventricular function. A year ago, he had an aortic valve replacement for severe aortic regurgitation. A few months after his operation, he was admitted with pulmonary edema. He was treated with diuretics and prior to discharge, commenced on ramipril and bisoprolol in view of their documented prognostic benefits in left ventricular dysfunction. 3 days later, he developed a symmetrical palpable purpuric eruption over both feet (Figs. 1 & 2). Subsequently the rash spread to the calves, and both feet became swollen and painful. Given the close temporal relationship between the rash and recent change in medications, it was felt that the rash could have been caused by bisoprolol or ramipril. As he had tolerated lisinopril previously, bisoprolol was thought to be the most likely culprit. The bisoprolol was stopped and the dose of ramipril was increased. Over the next two weeks, however, the rash became more extensive and he developed areas of ulceration around the toes and pre-ulcerative areas around the ankles. Ramipril was discontinued and he was prescribed symptomatic treatment for the skin. A full vasculitis screen was performed which showed no evidence of systemic involvement. Investigations to determine the cause of the vasculitis were also negative. His skin biopsy was deferred in view of the fact that he was on warfarin and had a metallic aortic valve. 3 weeks later, he had a further flare of vasculitis with new lesions and progressive ulceration. He was treated with prednisolone 20 mg daily and the rash and ulcers slowly resolved.
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
Discussion
ACE inhibitors are commonly prescribed drugs and are standard therapy in the management of hypertension and heart failure. Recognized adverse cutaneous effects include angioedema, bullous eruptions, urticaria, erythema multiforme, and vasculitis. Psoriasiform maculopapular and lichenoid eruptions have also been described. The mechanisms for ACE inhibitor-induced adverse reactions in the skin are mostly based on non-immunological mechanisms. By contrast, proposed mechanisms for drug-induced vasculitis are mainly immunological and include autoantibodies directed against drug-related haptens, drug toxicity against vessel walls, autoantibodies reacting with endothelial cells and cell mediated cytotoxic reactions against vessels, in addition to non-immunological mechanisms (1). Researchers have demonstrated the expression of a complete renin-angiotensin system in human skin, including the precursor of angiotensin II, angiotensinogen, renin, angiotensin converting enzyme, and receptors of the AT1 and AT2 receptor subtype, but their function is unknow (2). This patient developed cutaneous vasculitis after starting ramipril although he had previously tolerated lisinopril. Both ramipril and lisinopril are structurally similar and are part of the group of ACE inhibitors that are related to enalapril, which contains a dicarboxyl group. Lisinopril is an active molecule and ramipril is a pro-drug which is converted to an active diacid metabolite (ramiprilat). Previous exposure to lisinopril may have been the primary sensitizing event and reexposure to a structurally similar molecule (ramipril) could have resulted in the secondary allergic manifestations. As reexposure to immunogenic substances often results in a more severe reaction, the reintroduction of lisinopril was avoided in this case. Angiotensin II antagonists, however, are chemically different from ACE inhibitors and remain a therapeutic alternative.
References
1. Steckelings UM. Artuc T, Wollschlager T, et al. Angiotensin-converting Enzyme Inhibitors as Inducers of Adverse Cutaneous Reactions. Acta Derm Venereol 2001; 81:321-325.
2. Husgow T, Artuc M, Henz BM, et al. Normal skin as a potential source of Angiotensin II. Arch Dermatol Res 1998; 290:49.