Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.
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PMID:Four cases of tendinopathy in patients on statin therapy. 1170 10

Despite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the l-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the l-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane. Therefore, l-mevalonate pathway downstream products play critical roles in the different steps of an immune response including immune cell activation, migration, cytokine production, immune metabolism and survival. This review discusses the relevance of the different metabolites for the immunomodulatory effect of statins and connects preclinical results with data from clinical studies that tested statins for the treatment of different inflammatory diseases.
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PMID:Immune modulatory effects of statins. 2939 31