Rheumatology 2004; 43: 397-398
Rheumatology Vol. 43 No. 3 (c) British Society for Rheumatology 2003; all rights reserved
Letter to the Editor |
Statins and lupus erythematosus
Department of Dermatology, Centre Hospitalier Universitaire Vaudois, 1005 Lausanne, Switzerland
E-mail: bernard.noel{at}chuv.hospvd.ch
SIR, I read with interest the article of Wajed et al. [1] regarding the prevention of cardiovascular disease in systemic lupus erythematosus. Patients with systemic lupus erythematosus (SLE) have a high prevalence of cardiovascular diseases due to premature or accelerated atherosclerosis. Lowering cholesterol levels with statin therapy is one of the main targets in reducing the morbidity and mortality of SLE. However, these lipid-lowering agents may have unexpected immunological effects.
An increasing number of cases of statin-induced lupus like syndrome have recently been reported [2–4]. Most cases were caused by second-generation statins, such as simvastatin and atorvastatin. One case was associated with autoimmune hepatitis [5]. Statins have also been implicated in drug-induced dermatomyositis and other types of autoimmune skin diseases, such as lichen planus pemphigoides [6, 7]. In all cases of statin-induced lupus, skin eruption was similar to that occurring in subacute lupus erythematosus, with positive antinuclear antibodies. Unlike usual drug reactions, the skin eruption was observed only many months after the start of therapy and antinuclear antibodies were still positive many months after drug discontinuation. A causal relationship between drug intake and the autoimmune disease may be therefore difficult to establish.
Two pathogenic mechanisms may be suspected in statin-induced lupus-like syndrome. Cellular apoptosis, which plays a crucial role in SLE, may be exacerbated or triggered by second-generation statins, which are potent pro-apoptotic agents [8]. The release of nuclear antigens into the circulation may foster the production of pathogenic autoantibodies. The same mechanism is implicated with other environmental factors, such as ultraviolet light, which is a well-known triggering factor in SLE. The direct immunomodulator effect of statins on T lymphocytes is possibly also involved. SLE is characterized by a shifting of T helper 1 (Th1) to Th2 immune responses, leading to B-cell reactivity and the production of pathogenic autoantibodies. Statins may aggravate this phenomenon [9, 10].
Statins are among the most widely prescribed drugs. Their overall safety profile is good. However, these drugs have not only cholesterol-lowering properties but also have immunomodulator effects, which may potentially trigger or aggravate autoimmune diseases. Statin-induced lupus must be therefore considered in the differential diagnosis of SLE.
The author has declared no conflicts of interest.
References
- Wajed J, Ahmad Y, Durrington PN, Bruce IN. Prevention of cardiovascular disease in systemic lupus erythematosus—proposed guidelines for risk factor management. Rheumatology Advance Access, 16 July 2003.
- Bannwarth B, Miremont G, Papapietro PM. Lupuslike syndrome associated with simvastatin. Arch Intern Med 1992;152:1093.
[Abstract/Free Full Text] - Hanson J, Bossingham D. Lupus-like syndrome associated with simvastatin. Lancet 1998;352:1070.[Web of Science][Medline]
- Srivastana M, Rencic A, Diglio G et al. Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Arch Dermatol 2003;139:45–9.
[Abstract/Free Full Text] - Graziadei IW, Obermoser GE, Sepp NT, Erhart KH, Vogel W. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus 2003;12:409–12.
[Abstract/Free Full Text] - Noël B, Cerottini JP, Panizzon RG. Atorvastatin-induced dermatomyositis. Am J Med 2001;110:670–1.[CrossRef][Web of Science][Medline]
- Stoebner PE, Michot C, Ligeron C, Durand L, Meynadier J, Meunier L. Lichen plan pemphigoïde induit par la simvastatine. Ann Dermatol Venereol 2003;130:87–90.
- Knapp AC, Huang J, Starling G, Kiener PA. Inhibitors of HMG-CoA reductase sensitize human smooth muscle cells to Fas-ligand and cytokine-induced cell death. Atherosclerosis 2000;152:217–27.[CrossRef][Web of Science][Medline]
- Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nature Med 2000;6:1399–140.[CrossRef][Web of Science][Medline]
- Youssef S, Stuve O, Patarroyo JC et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002;420:78–84.[CrossRef][Medline]
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