Statin Adverse Effects FAQ: LUPUS-LIKE SYMPTOMS AND STATINS, EXERCISE
INTOLERANCE

To my physician,

I believe that my symptoms may be due to the adverse effects a_ssociated
with cholesterol-lowering statin drugs.  I need your help to understand the
cause of my symptoms, treatment options, and the prognosis for my recovery.

Please review the references below, published medical studies that show
similar problems a_ssociated with statin drugs.  These are made available
via the National Institutes of Health (NIH,
http://www.ncbi.nlm.nih.gov/Entrez/) library of biomedical journal citations
and other major repositories of medical research.

Also, I am respectfully requesting that you file an adverse effects report
with the FDA (http://www.fda.gov/medwatch/how.htm), and that you please send
a copy of the report to the to the NIH-funded Statin Study, attention: Dr.
Beatrice Golomb, Principal Investigator.
Statin Study website: http://medicine.ucsd.edu/statin/
Statin Study contact info: http://medicine.ucsd.edu/statin/contactinfo.html
UCSD STATIN STUDY E-MAIL ADDRESS: statinstudy@ucsd.edu
MAILING ADDRESS: UCSD Statin Study 9500 Gilman Dr. La Jolla, CA 92093-0995
PHONE NUMBER: (858) 558-4950

Thank you

LUPUS-LIKE SYMPTOMS AND STATINS, EXERCISE INTOLERANCE

References (updated as of  January 7, 2005):

Drug-induced lupus-like syndrome a_ssociated with severe autoimmune
hepatitis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1
2765306&dopt=Abstract
Graziadei IW, Obermoser GE, Sepp NT, Erhart KH, Vogel W.
Lupus. 2003;12(5):409-12.
PMID: 12765306 [PubMed - in process]

"Atorvastatin and other members of the statin family are widely used for the
treatment of hypercholesterolaemia in order to reduce the risk of
atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse
events are mostly mild and only a few cases of lupus-like syndrome or severe
acute hepatitis have been documented. In this case report we describe a
patient who developed an atorvastatin-induced severe autoimmune hepatitis.
In addition, this patient presented with a concomitant systemic lupus-like
syndrome which has been already described for statins but not in
a_ssociation with severe liver disease. Although the drug was immediately
withdrawn the disease persisted and even deteriorated to a fulminant disease
with evidence of acute hepatic failure. The patient failed to respond to
conventional immunosuppression with corticosteroids and azathioprine. Only
the introduction of intense immunosuppressive therapy, as used in solid
organ transplantation, led to a complete and sustained recovery of the
patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which
are well-known genetic factors a_ssociated with autoimmune diseases. This
case is the first report of a drug-induced lupus-likesyndrome concomitant
with a severe autoimmune hepatitis in a genetically predisposed patient."

Noel B, Panizzon RG.  Lupus-like syndrome a_ssociated with statin
therapy.Dermatology. 2004;208(3):276-7. PMID: 15118389 [PubMed - indexed for
MEDLINE]"Statins are among the most widely prescribed drugs. An increasing
number of lupus-like syndrome has recently been reported with these
lipid-lowering agents. We describe a new case a_ssociated with simvastatin
therapy. The presence of anti-dsDNA antibodies in the serum is for the first
time reported confirming that statins may also induce a systemic autoimmune
reaction. Statin-induced lupus-like syndrome is characterized by the long
delay between the beginning of therapy and the skin eruption. Antinuclear
antibodies may persist for many months after drug discontinuation. The
causal relationship may be therefore difficult to establish, and probably
many cases are unrecognized. Early diagnosis may avoid unnecessary
immunosuppressive therapy. Copyright 2004 S. Karger AG, Basel" Lantuejoul S,
Brambilla E, Brambilla C, Devoua_ssoux G.  Statin-induced fibrotic
nonspecific interstitial pneumonia.Eur Respir J. 2002 Mar;19(3):577-80.
PMID: 11936540 [PubMed - indexed for MEDLINE]"Statins inhibit the
3-hydroxy-3-methylglutaryl coenzyme A reductase, reduce the serum level of
low-density lipoprotein cholesterol, and are extensively prescribed to
prevent cardiovascular mortality and morbidity. Few systemic adverse
effects, such as pseudopolymyositis, lupus-like syndromes, and anecdotal
hypersensitivity pneumonitis, have been reported. A simvastatin-induced
diffuse interstitial pneumonia a_ssociated with a nonspecific interstitial
pneumonia pattern at histological analysis is repoted here. Ultrastructural
analysis showed a diffuse cytoplasmic accumulation of intralysosomial
lamellar inclusions in type II pneumonocytes, histiocytes and endothelial
cells, suggesting a shared pathogenesis with amphiphilic drug-induced toxic
lung injury. Because statins are increasingly prescribed, statin-induced
interstitial lung disorders may be more frequently observed and early
recognition will be required." Chazerain P, Hayem G, Hamza S, Best C, Ziza
JM.  Four cases of tendinopathy in patients on statin therapy.Joint Bone
Spine. 2001 Oct;68(5):430-3. PMID: 11707010 [PubMed - indexed for MEDLINE]"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 cla_ss 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."

Malignant hyperthermia susceptibility revealed by increased serum creatine
kinase concentrations during statin treatment.
Krivosic-Horber R, Depret T, Wagner JM, Maurage CA.
Eur J Anaesthesiol. 2004 Jul;21(7):572-4.
Publication Types:  Case Reports, Letter

PMID: 15318472 [PubMed - indexed for MEDLINE]  Metabolic intolerance to
exercise
[Article in Spanish]
Arenas J, Martin MA.
Neurologia. 2003 Jul-Aug;18(6):291-302.
Laboratorio de enfermedades mitocondriales y nurometabolicas, Centro de
Investigacion Hospital Universitario 12 de Octubre, Madrid, Spain.
jarenas@h12o.es
"Exercise intolerance (EI) is a frequent cause of medical attention,
although it is sometimes difficult to come to a final diagnosis. However,
there is a group of patients in whom EI is due to a metabolic dysfunction.
McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL)
deficiency. The ischemic exercise test shows a flat lactate curve. The most
frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL
deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II
deficiency is invariably a_ssociated to repetitive episodes of myoglobinuria
triggered by exercise, cold, fever or fasting. The diagnosis depends on the
demonstration of CPT II deficiency in muscle. The most frequent mutation in
the CPT2 gene is the S113L. Patients with muscle adenylate deaminase
deficiency usually show either a mild myopathy or no symptom. The diagnosis
is based on the absence of enzyme activity in muscle and the lack of rise of
ammonia in the forearm ischemic exercise test. The mutation Q12X in the
AMPD1 gene is strongly a_ssociated with the disease. Exercise intolerance is
a common complaint in patients with mitochondrial respiratory chain (MRC)
deficiencies, although it is often overshadowed by other symptoms and signs.
Only recently we have come to appreciate that exercise intolerance can be
the sole presentation of defects in the mtDNA, particularly in complex I,
complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be
observed in patients under statin treatment, particularly if a_ssociated
with fibrates, due to an alteration in the a_ssembly of the complex IV of
the MRC."
Publication Types: Review, Review, Tutorial

PMID: 12838448 [PubMed - indexed for MEDLINE]