Giant Cell Arteritis and Polymyalgia Rheumatica After Reexposure to a Statin: A Case Report

Background: Statins, or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are widely used to prevent cardiovascular diseases and are generally regarded as safe. However, adverse reactions, such as myalgia, myositis, rhabdomyolysis, muscle weakness, and cramps with or without elevated serum creatine kinase levels, may occur (1). Furthermore, we have recently described that statins may also be associated with polymyalgia rheumatica (PMR) (2). Case Report: A 78-year-old woman presented in December 2003 with muscle pain in the hips and shoulders and morning stiffness. She had a history of hypercholesterolemia treated with atorvastatin, 10 mg/d, for 9 months and hypertension treated with candesartan, 8 mg/d, and bisoprolol, 2.5 mg/d. Laboratory studies revealed an erythrocyte sedimentation rate (ESR) of 61 mm/h and a platelet count of 487109 cells/L. The patient was diagnosed with PMR and advised to stop atorvastatin therapy. Her symptoms gradually resolved. Five months after presentation, ESR was normal at 13 mm/h. In February 2006, her low-density lipoprotein cholesterol level was 4.5 mmol/L (174 mg/dL), and therapy with rosuvastatin, 5 mg twice weekly, was resumed. Symptoms of PMR recurred and progressed, and she reported visual disturbances. Temporal arteries were tender on palpation. Hematoxylineosin staining of a biopsy specimen of the temporal artery showed panarteritis comprising lymphocytes, neutrophils, eosinophils, and macrophages with giant cells (Figure 1). Intimal thickening with clear luminal narrowing was also noted (Figure 2). An ESR of 95 mm/h and a C-reactive protein level of 2381.0 nmol/L were found on laboratory studies. Giant cell arteritis (GCA) with PMR was diagnosed. Figure 1. Inflammatory cells. Hematoxylineosin stain showing lymphocytes (blue arrow), eosinophils (red arrow), and macrophages and giant cells (black arrow) (original magnification,100). Figure 2. Panarteritis. Hematoxylineosin stain showing panarteritis of the temporal artery (original magnification,200). Rosuvastatin therapy was discontinued, and the patient was treated with prednisolone, 40 mg/d, the dosage of which was slowly tapered. Her symptoms abated over the next few months, and the ESR and C-reactive protein level decreased to 6 mm/h and less than 95.2 nmol/L, respectively. In June 2008, prednisolone therapy was stopped. A few months later, PMR and GCA relapsed. This time, relapse was not preceded by statin therapy. The patient again received corticosteroids, which resulted in a good response until she died in February 2009. Discussion: The patient's presentation strongly suggested statin-induced PMR and GCA. Both are part of the same disease spectrum and are associated with the HLA-DRB1*04 allele (3), the presence of which was not determined in this patient. Between 16% and 21% of patients with PMR have GCA (3). Of note, PMR in this patient resolved after statin therapy was discontinued and PMR and GCA recurred after statin therapy (that is, rosuvastatin) was resumed. This sequence of events suggests that statins may trigger PMR and GCA in sensitive patients. However, this patient relapsed later without a preceding statin challenge, showing that the disease process had become independent of the external trigger, which often occurs in drug-induced vasculitis (4). The mechanism of statin-associated PMR and GCA is not clear. Because many patients receiving statins develop myalgia and/or more severe muscle disease (1), mild myopathic damage probably plays a role in statin-associated PMR and GCA. In statin-associated necrotizing myopathy, these drugs have recently been postulated to induce neoantigens as a result of muscle damage, which are subsequently presented to the immune system. A similar mechanism may operate in statin-associated PMR and GCA (2). Indeed, in an animal model we recently showed that statin use leads to dysregulation of immune responses, possibly resulting in autoimmunity (5). In summary, we report the first case to our knowledge of GCA combined with PMR that was probably induced by a statin, rosuvastatin. Of interest, in this patient, previous use of atorvastatin had been followed by a first episode of PMR. We propose that PMR should be suspected when a patient receiving statin therapy presents with myalgia of the hips and shoulders combined with morning stiffness.