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Atorvastatin-induced dermatomyositis

2001; Elsevier BV; Volume: 110; Issue: 8 Linguagem: Inglês

10.1016/s0002-9343(01)00711-2

1555-7162

Bernard Noël, Jean‐Philippe Cerottini, Renato G. Panizzon,

Skin Diseases and Diabetes

Myositis and rhabdomyolysis are rare, dose-related complications of statins (HMG-CoA reductase inhibitors). We report a case of dermatomyositis associated with atorvastatin, a potent second-generation statin. A 44-year-old man was hospitalized for the progressive appearance of dysphagia, dysphonia, and severe asthenia. He had been treated for 1 year with atorvastatin (10 mg/day) for a familial hypercholesterolemia. Examination showed a typical facial heliotrope rash, a violaceous erythema that was more pronounced in a photodistributed area, characteristic papules of Gottron with periungual telangiectasia, skin necrotic lesions of the left ear, and severe proximal muscle paresia. Complete blood count, coagulation and liver function tests, as well as renal clearance were all in the normal range. The serum creatine kinase level was elevated (>2000 U/liter). A positive antinuclear antibody titer greater than 1:2560 with a nucleolar pattern was observed. There were no antibodies to DNA or extractable nuclear antigen or histone. Investigation for an underlying neoplasm was negative. Keratinocytes apoptosis with liquefaction of the epidermal basal zone was seen on skin biopsy, and severe necrosis of the segmental muscle fibers with perifascicular T lymphocytes, predominantly of the CD4 helper-inducer phenotype, was observed on muscle biopsy. Direct immunofluorescence examination of the skin and muscle was nonspecific. There was no sign for a vasculitis. After the atorvastatin was discontinued, the clinical improvement was rapid and spontaneous. Normalization of serum creatine kinase but not of antinuclear antibodies was observed. Nine months after drug discontinuation, the antinuclear antibody titer remained greater than 1:2,560 despite a normal serum creatine kinase level and the absence of skin lesions. With the use of potent second-generation statins, an increasing number of cases of drug-induced lupus erythematosus have been reported (1Bannwarth B. Miremont G. Papapietro P.M. Lupuslike syndrome associated with simvastatin.Arch Intern Med. 1992; 152: 1093Crossref PubMed Scopus (39) Google Scholar, 2Hanson J. Bossingham D. Lupus-like syndrome associated with simvastatin.Lancet. 1998; 352: 1070Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 3Khosla R. Butman A.N. Hammer D.F. Simvastatin-induced lupus erythematosus.South Med J. 1998; 91: 873-874Crossref PubMed Scopus (28) Google Scholar, 4Ahmad A. Fletcher M.T. Roy T.M. Simvastatin-induced lupus-like syndrome.Tenn Med. 2000; 93: 21-22PubMed Google Scholar). Only two cases of statin-induced dermatomyositis have been published; one was associated with pravastatin and the other with simvastatin (5Schalke B.B. Schmidt B. Toyka K. Hartung H.P. Pravastatin-associated inflammatory myopathy.N Engl J Med. 1992; 327: 649PubMed Google Scholar, 6Khattak F.H. Morris I.M. Branford W.A. Simvastatin-associated dermatomyositis.Br J Rheumatol. 1994; 33: 199Crossref PubMed Scopus (63) Google Scholar). Keratinocytes apoptosis with liquefaction of the epidermal basal zone are found in both lupus erythematosus and dermatomyositis (7Pablos J.L. Santiago B. Galindo M. et al.Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis.J Pathol. 1999; 188: 63-68Crossref PubMed Scopus (72) Google Scholar). Persistent positive antinucelar antibodies were also observed in statin-induced lupus erythematosus long after the drug was discontinued. A common physiopathologic mechanism involving karatinocyte apoptosis with autoantibodies induction can be suspected (7Pablos J.L. Santiago B. Galindo M. et al.Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis.J Pathol. 1999; 188: 63-68Crossref PubMed Scopus (72) Google Scholar, 8Rovere P. Sabbadini M.G. Fazzini F. et al.Remnants of suicidal cells fostering systemic autoaggression. Apoptosis in the origin and maintenance of autoimmunity.Arthritis Rheum. 2000; 43: 1663-1672Crossref PubMed Scopus (75) Google Scholar). Statins are potent inducers of apoptosis, but a direct immunomodulator effect on T-lymphocytes has also been observed (9Guijarro C. Blanco-Colio L.M. Ortego M. et al.3-Hydroxy-3-methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.Circ Res. 1998; 83: 490-500Crossref PubMed Scopus (394) Google Scholar, 10Kwak B. Mulhaupt F. Myit S. Mach F. Statins as a newly recognized type of immunomodulator.Nature Med. 2000; 6: 1399-1402Crossref PubMed Scopus (1253) Google Scholar). Further studies are warranted to evaluate the exact mechanism of statin-induced autoimmunity, as well as its long-term clinical significance. Two important clinical implications can be drawn from this case report. First, high plasma levels of antinuclear antibody may be due to statins long after patients stop taking them. Second, screening for both plasma creatine kinase concentration and antinuclear antibody may be useful in patients treated with these lipid-lowering agents in cases of unexplained fatigue or skin eruption.