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Inflammatory myopathy and severe rhabdomyolysis induced by leuprolide acetate therapy for prostate cancer: a case report
© Bergner et al; licensee BioMed Central Ltd. 2011
Received: 31 March 2011
Accepted: 24 August 2011
Published: 24 August 2011
Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone used for the treatment of prostate cancer. Its side effects are hot flashes, nausea, and fatigue. We report a case of a patient with proximal inflammatory myopathy accompanied by severe rhabdomyolysis and renal failure following the second application of leuprolide acetate. Drug withdrawal and steroid therapy resulted in remission within six weeks of the diagnosis. To the best of our knowledge, our case report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis and renal failure in the literature.
A 64-year-old Swiss Caucasian man was admitted to the hospital because of progressive proximal muscle weakness, dyspnea, and oliguria. He had been treated twice with leuprolide acetate in monthly doses. We performed a muscle biopsy, which excluded other causes of myopathy. The patient's renal failure and rhabdomyolysis were treated with rehydration and steroid therapy.
The aim of our case report is to highlight the rare but severe side effects associated with leuprolide acetate therapy used to treat patients with inflammatory myopathy: severe rhabdomyolysis and renal failure.
The etiology of myopathy includes congenital disorders, immunologic processes, malignancies, infections, endocrinopathies, alcohol ingestion and adverse drug reactions (particularly statins), immunosuppressive agents, and nucleoside analog reverse transcriptase inhibitors [1–5]. Drugs can exert myotoxic effects on muscles through mechanisms that are direct (for example, alcohol ingestion, statins, or anti-malarial agents), immunological (for example, interferon α), or indirect (for example, drug-induced hypokalemia, hyperthermia, or seizures). Myositis can be associated with different cancers, mainly lung and breast cancers, but also prostate cancer. In one study, cancer was diagnosed in 9% of 396 patients with polymyositis, and of the 168 men with polymyositis, four had prostate cancer . In another study, of 309 patients with dermatomyositis or polymyositis, 11.9% had cancer and one of these had prostate cancer . Myopathy might affect all muscles or only proximal muscles, as well as pharyngeal muscles.
The patient was rehydrated with bicarbonate solution until his jugular veins were distended, and therapy with intravenous furosemide, ceftriaxone, methylprednisolone (500 mg/day), calcium, vitamin D, and alendronate was initiated. The patient's proximal muscle weakness declined within three days. Within four days, his serum creatinine level rose to 190 μmol/L, which was accompanied by oliguria, and his serum creatine kinase level dropped from a maximum of 169,910 U/L to 34,897 U/L. His steroid therapy was modified to oral prednisone 80 mg/day. Seven days later he could walk again with support, and his urine output and serum creatinine level had normalized. After 28 days, his prednisone treatment was tapered back to 35 mg/day, but within four days his serum creatine kinase rose again from 547 U/L to 1548 U/L without clinical deterioration. His prednisone dosage was increased to 70 mg/day, and his serum creatine kinase declined to normal (246 U/L) within six weeks. The patient was discharged from the hospital free of symptoms after undergoing orchiectomy on the 45th day following his initial admission. His serum creatine kinase and serum creatinine were normal, and he was prescribed prednisone 50 mg/day. After his discharge from the hospital, prednisone was tapered to 20 mg/day and his serum creatine kinase level rose slightly without clinical relapse. Nine months after discharge his prednisone therapy was stopped without a subsequent increase in his creatine kinase level. At his 12-month follow-up examination, the patient was in good clinical condition and had normal laboratory values, including PSA.
Myopathy with rhabdomyolysis and renal failure can have several causes. In the course of searching for a possible inflammatory myopathy, we found no clinical or serological signs of endocrinopathies, viral infections, or connective tissue diseases and no immunohistochemical signs of autoimmune polymyositis or dermatomyositis. The negative results of screening of our patient for these antibodies represent an additional argument against a diagnosis of autoimmune polymyositis, although anti-Jo-1 antibodies are found in 18% to 55% of these patients, anti-Mi-2 antibodies are found in 4% to 9%, anti-SRP antibodies are found in 4.8% to 11% of patients with autoimmune polymyositis, and anti-PM-Scl antibodies are found in 25% of patients with concomitant polymyositis and scleroderma [8–10]. Although cancer-associated myopathy can be of inflammatory origin , we assume that a paraneoplastic etiology of the myositis in our patient is not probable. While cancer-associated myositis can ameliorate during cancer treatment , the treatment of cancer in our patient resulted in the development of clinical signs of myopathy. On the basis of his serum PSA and the fact that the size of the solitary node in his lung decreased during leuprolide acetate therapy, we assume that prostate cancer therapy was successful in our patient.
We consider leuprolide acetate to be the cause of myopathy in our patient. We did not find an infectious cause of his myopathy. However, T lymphocytes were found. Thus, it is likely that a drug-induced T-lymphocyte-mediated mechanism, not a direct toxic effect of leuprolide acetate, caused his muscle necrosis. We cannot explain the exact mechanism. Further studies are required to answer this question.
To the best of our knowledge, this is the fourth such case reported in the literature. The three previously published cases manifested with proximal myopathy. While the muscle biopsy in the first case showed diffuse T-lymphocyte infiltration of the muscle and was treated with steroids , the biopsy in the second case revealed only mild, non-specific changes . In the third case, no biopsy was performed . In these three studies, the reported serum creatine kinase values were 2728 U/L, normal, and 1290 U/L, respectively, and within one to six months after leuprolide acetate therapy was discontinued, the patients' symptoms of myopathy vanished. Renal failure did not occur.
In this case report, we highlight rare but severe side effects of leuprolide acetate therapy: inflammatory myopathy, severe rhabdomyolysis, and renal failure. To the best of our knowledge, this report describes the second case of leuprolide acetate-induced inflammatory myopathy and the first case of severe leuprolide acetate-induced rhabdomyolysis with renal failure.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
We thank Professor Dr M Tolnay and Dr D Pfeiffer for providing us the histological images.
- Klopstock T: Drug induced myopathies. Curr Opin Neurol. 2008, 21: 590-595. 10.1097/WCO.0b013e32830e2774.View ArticlePubMedGoogle Scholar
- Buchbinder R, Forbes A, Hall S, Denett X, Giles G: Incidence of malignant disease in biopsy-proven inflammatory myopathy. Ann Intern Med. 2001, 134: 1087-1095.View ArticlePubMedGoogle Scholar
- Stockton D, Doherty VR, Brewster DH: Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study. Br J Cancer. 2001, 85: 41-45. 10.1054/bjoc.2001.1699.View ArticlePubMedPubMed CentralGoogle Scholar
- Bannwarth B: Drug-induced myopathies. Expert Opin Drug Saf. 2002, 1: 65-70. 10.1517/14740318.104.22.168.View ArticlePubMedGoogle Scholar
- Bannwarth B: Drug-induced musculoskeletal disorders. Drug Saf. 2007, 30: 27-46. 10.2165/00002018-200730010-00004.View ArticlePubMedGoogle Scholar
- Sigurgeirsson B, Lindelöf B, Edhag O, Allander E: Risk of cancer in patients with dermatomyositis or polymyositis. N Engl J Med. 1992, 326: 363-367. 10.1056/NEJM199202063260602.View ArticlePubMedGoogle Scholar
- András C, Ponyi A, Constantin T, Csiki Z, Szekanecz E, Szodoray P, Dankó K: Dermatomyositis and polymyositis associated with malignancy: a 21-year retrospective study. J Rheumatol. 2008, 35: 438-444.PubMedGoogle Scholar
- Targoff IN: Autoantibodies and their significance in myositis. Curr Rheumatol Rep. 2008, 10: 333-340. 10.1007/s11926-008-0053-2.View ArticlePubMedGoogle Scholar
- Targoff IN: Myositis specific autoantibodies. Curr Rheumatol Rep. 2006, 8: 196-203. 10.1007/s11926-996-0025-3.View ArticlePubMedGoogle Scholar
- Ghirardello A, Zampieri S, Tarricone E, Iaccarino L, Bendo R, Briani C, Rondinone R, Sarzi-Puttini P, Todesco S, Doria A: Clinical implications of autoantibody screening in patients with autoimmune myositis. Autoimmunity. 2006, 39: 217-221. 10.1080/08916930600622645.View ArticlePubMedGoogle Scholar
- Levine SM: Cancer and myositis: new insights into an old association. Curr Opin Rheumatol. 2006, 18: 620-624. 10.1097/01.bor.0000245721.02512.77.View ArticlePubMedGoogle Scholar
- Crayton H, Bohlmann T, Sufit R, Graziano FM: Drug induced polymyositis secondary to leuprolide acetate (Lupron) therapy for prostate carcinoma. Clin Exp Rheumatol. 1991, 9: 525-528.PubMedGoogle Scholar
- Van Gerpen JA, McKinley KL: Leuprolide-induced myopathy. J Am Geriatr Soc. 2002, 50: 1746-1747. 10.1046/j.1532-5415.2002.50474.x.View ArticlePubMedGoogle Scholar
- Salvador Hernández J, Ferrera Rodríguez R, Martín Oliva MV: LH-RH analogues and myopathy in Spanish. Aten Primaria. 2004, 34: 265-10.1157/13066407.View ArticlePubMedGoogle Scholar
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