Polymyalgia, Hypersensitivity Pneumonitis and Other Reactions in Patients Receiving HMG-CoA Reductase Inhibitors: A Report of Ten Cases

doi:10.1378/chest.115.3.886

Chest

Volume 115, Issue 3, March 1999, Pages 886-889

https://doi.org/10.1378/chest.115.3.886 Get rights and content

Since 1980, hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have become the most prescribed cholesterol-lowering drugs. They are effective and have been shown to lower the incidence of stroke, cardiovascular disease, and mortality.¹ By inhibiting the HMG-CoA reductase, which is a rate-limiting enzyme in the biosynthesis of cholesterol, these drugs increase the number of low-density lipoprotein receptors in the liver and, therefore, decrease serum low-density lipoprotein cholesterol. They have an excellent safety profile with a low frequency of side effects.² Recently we have encountered a series of patients with evidence of hypersensitivity to HMG-CoA reductase inhibitors, or statin drugs. We are reporting our experience with 10 patients: two with potentially life-threatening reactions and one with biopsy evidence of hypersensitivity pneumonitis. We are aware of only two previous cases of interstitial lung disease in association with statin medications.³ ^,4

Section snippets

Materials and Methods

We are reporting the experience of a multispecialty clinic and a solo practitioner cardiologist (HJG). Patient 1 presented with urticaria and angioedema in 1996. His antinuclear antibody (ANA) test was positive, and lovastatin was the only medication he was taking. Therefore, the suspicion was that this medication was responsible for his symptoms because they resolved immediately on withdrawal of the medication. Subsequently, we became vigilant for similar reactions and encountered an

Patient 1

A 54-year-old man had bypass surgery 9 years ago followed by a recent angioplasty. Nine months after starting lovastatin, 20 mg daily, for hypercholesterolemia, he developed urticaria over his entire body and angioedema of his upper lip. The serum complement studies and erythrocyte sedimentation rate (ESR) were normal, and the ANA test was positive at 1:320 homogeneous. He had eosinophilia measuring 4.3%. He was treated with cetirazine, 10 mg daily. Lovastatin was discontinued, and his symptoms

Discussion

HMG-CoA reductase inhibitors are among the most frequently prescribed medications with proven efficacy and infrequent side effects.² Any incidence of hypersensitivity is unknown with these drugs. Based on known pharmaceutical data from our community, we estimate that the incidence of hypersensitivity in our population is approximately 0.1%. This estimate was made from prescription records in a managed-care setting. Manufacturers of statin drugs report the combined incidence of rash and allergic

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It has also been reported with the use of other antihypertensive agents, such as angiotensin receptor blockers,195 calcium channel blockers,196 and hydrochlorothiazide,197 as well as antiplatelet agents, such as thienopyridine and clopidogrel.198 The use of the statin class of medications, including simvastatin, fluvastatin, atorvastatin, and pravastatin, is infrequently associated with this side effect.199-202 A number of chemotherapy and immunomodulating agents have been shown to increase the risk of lymphoproliferative disorders and neoplasms.203
Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice.
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The myalgias typically resolve within 2 months of discontinuing the statin. Statin-related muscular complaints may aggravate pre-existing myofascial pain in patients with fibromyalgia10-12 and may trigger polymyalgia rheumatica-like symptoms.13,14 These classic features should be borne in mind when evaluating the many types of atypical symptoms sometimes suspected of being statin-associated.
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Chest

Selected ReportsPolymyalgia, Hypersensitivity Pneumonitis and Other Reactions in Patients Receiving HMG-CoA Reductase Inhibitors: A Report of Ten Cases

Section snippets

Materials and Methods

Patient 1

Discussion

J Allergy Clin Immunol

Arch Biochem Biophys

Biochem Biophys Res Commun

Cholesterol lowering with statin drugs, risk of stroke, and total mortality: an overview of randomized trials

JAMA

HMG-CoA reductase inhibitors for treatment of hypercholesterolemia

N Engl J Med

Selected Reports
Polymyalgia, Hypersensitivity Pneumonitis and Other Reactions in Patients Receiving HMG-CoA Reductase Inhibitors: A Report of Ten Cases