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| {{Infobox medical condition (new) | | |
| | name = Statin-associated Autoimmune Myopathy | | {{Infobox medical condition |
| | synonyms = Anti-HmG Coenzyme A Reductase Myopathy, Immune-mediated necrotizing myopathy associated with statins, Statin-associated immune-mediated myopathy, Statin-induced autoimmune myositis, Statin-induced necrotizing autoimmune myopathy | | | name = Statin-associated autoimmune myopathy |
| | image =
| | | synonyms = Statin-induced necrotizing autoimmune myopathy |
| | caption =
| | | field = [[Rheumatology]], [[Neurology]] |
| | alt =
| | | symptoms = [[Muscle weakness]], [[Myalgia]], [[Fatigue (medical)]], [[Elevated creatine kinase]] |
| | field = [[Rheumatology]] | | | onset = Typically after [[statin]] therapy |
| | symptoms = Muscle weakness | | | duration = Chronic |
| | onset = | | | causes = [[Autoimmune disease]] triggered by [[statin]] use |
| | duration = | | | risks = Use of [[statin]] medications |
| | causes = | | | diagnosis = [[Muscle biopsy]], [[Blood test]] for [[anti-HMGCR antibodies]] |
| | risks = | | | differential = [[Polymyositis]], [[Dermatomyositis]], [[Inclusion body myositis]] |
| | diagnosis = | | | treatment = [[Immunosuppressive drug]]s, [[Corticosteroid]]s, discontinuation of [[statin]]s |
| | differential = | | | prognosis = Variable, can be chronic |
| | prevention =
| | | frequency = Rare |
| | treatment = [[Corticosteroid]]s, [[immunosuppressive medication]]s, withdrawal of implicated [[statin]] | |
| | medication =
| |
| | prognosis = | |
| | frequency = Rare | |
| | deaths =
| |
| }} | | }} |
| <!-- Definition and symptoms -->
| | {{Short description|A rare autoimmune condition associated with statin use}} |
| '''Statin-associated autoimmune myopathy (SAAM)''' is a very rare but serious form of [[myopathy|muscle damage]] caused by the [[immune system]] in people who take [[statin]] medications.<ref name="Thompson2016">{{cite journal |last1=Thompson |first1=PD |last2=Panza |first2=G |last3=Zaleski |first3=A |last4=Taylor |first4=B |title=Statin-Associated Side Effects |journal=Journal of the American College of Cardiology |date=May 2016 |volume=67 |issue=20 |pages=2395–2410 |doi=10.1016/j.jacc.2016.02.071 |pmid=27199064 |type=Review}}</ref> | | '''Statin-associated autoimmune myopathy''' (SAAM) is a rare [[autoimmune disease]] that occurs in some individuals who are treated with [[statins]], a class of drugs commonly used to lower [[cholesterol]] levels in the blood. This condition is characterized by muscle weakness and elevated levels of [[creatine kinase]] (CK) in the blood, indicating muscle damage. |
| | | ==Pathophysiology== |
| The exact cause is unclear. No particular statin has been associated with SAAM more than others.<ref name="Hamann2013"/> SAAM is diagnosed by a combination of consistent findings on physical examination, the presence of anti HMG-CoA reductase antibodies in a person with myopathy, evidence of muscle breakdown, and [[muscle biopsy]].<ref name="Mammen2016"/>
| | Statins are known to inhibit the enzyme [[HMG-CoA reductase]], which plays a crucial role in the [[mevalonate pathway]] of [[cholesterol synthesis]]. In some individuals, the use of statins can trigger an autoimmune response against [[HMG-CoA reductase]] itself, leading to muscle inflammation and damage. This autoimmune response is mediated by [[autoantibodies]] that target the enzyme, resulting in muscle weakness and myopathy. |
| | | ==Clinical Presentation== |
| Treatment involves stopping the associated statin medication and taking medication to [[immunosuppression|suppress the immune system]].
| | Patients with statin-associated autoimmune myopathy typically present with progressive muscle weakness, particularly in the proximal muscles such as those of the shoulders and hips. This weakness can lead to difficulties in performing everyday activities such as climbing stairs, lifting objects, or rising from a seated position. Muscle pain may also be present, although it is not as prominent as the weakness. |
| | |
| SAAM is a very rare disorder with an estimated [[Prevalence (epidemiology)|prevalence]] of 2-3 cases in 100,000 treated individuals and appears to be more common in people over the age of 50.<ref name="Mammen2016">{{cite journal |last1=Mammen |first1=AL |title=Statin-Associated Autoimmune Myopathy |journal=New England Journal of Medicine |date=February 2016 |volume=374 |issue=7 |pages=664-9 |doi=10.1056/NEJMra1515161 |pmid=26886523|type=Review}}</ref>
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| ==Signs and symptoms==
| |
| SAAM is characterized by severe symmetric proximal muscle weakness (shoulders, upper arms, thighs), very high blood levels of [[creatine kinase]] (CK) from [[skeletal muscle]] breakdown, and persistent symptoms and CK elevation despite stopping the offending [[statin]] medication.<ref name="Thompson2016"/><ref name="Mammen2016"/> This differs from other forms of statin [[myopathy]] that are expected to resolve following withdrawal of the statin.<ref name="Thompson2016"/> Mild [[arthralgia|joint pain]] and rash may be present.<ref name="Mammen2016"/> In people affected by SAAM, the median duration of statin therapy was 38 months prior to the onset of muscular symptoms.<ref name="Christopher2017"/> This indicates that SAAM can affect people who have taken a statin for a long period of time even if they had no previous muscular side effects.<ref name="Christopher2017">{{cite journal |last1=Christopher-Stine |first1=L |last2=Basharat |first2=P |title=Statin-associated immune-mediated myopathy: biology and clinical implications. |journal=Current Opinion in Lipidology |date=April 2017 |volume=28 |issue=2 |pages=186-92 |doi=10.1097/MOL.0000000000000399 |pmid=28207435|type=Review}}</ref>
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| ==Pathogenesis== | |
| It is unclear precisely how statins lead to statin-associated autoimmune myopathy.<ref name="Thompson2016"/> The disorder has been positively associated with [[HLA-DR11]] and the DRB1*11:01 [[allele]].<ref name="Thompson2016"/> There are likely as of yet other unidentified genetic and environmental risk factors associated with SAAM given the prevalence of the DRB1 allele and the low incidence of autoimmunity in that group.<ref name="Mammen2016"/> Statins effectively lower [[cholesterol]] levels in the blood by inhibiting the [[HMG-CoA reductase]] [[enzyme]] activity; however, by doing this, they also increase production of the HMG-CoA reductase protein.<ref name="Thompson2016"/> In genetically susceptible individuals, it is hypothesized that this increase in production of HMG-CoA reductase may lead to abnormal processing of this protein and subsequent generation of antibodies against it resulting in SAAM.<ref name="Thompson2016"/> Another theory postulates that the configuration of the HMG-CoA reductase protein may change when statin medications bind to it causing the protein to expose certain [[antigen]]s that the immune system is not tolerant to resulting in the production of antibodies against it.<ref name="Mammen2016"/>
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| ==Diagnosis== | | ==Diagnosis== |
| Statin exposure followed by the development of necrotizing myopathy is insufficient to make the diagnosis. Alternate causes of [[myositis]] and necrotizing myopathy must first be excluded.<ref name="Hamann2013"/> A [[muscle biopsy]] consistent with SAAM will demonstrate [[necrosis|muscle cell death]] with muscle fiber regeneration and typically has few inflammatory cells.<ref name="Hamann2013">{{cite journal |last1=Hamann |first1=PD |last2=Cooper |first2=RG |last3=McHugh |first3=NJ |last4=Chinoy |first4=H |title=Statin-induced necrotizing myositis - a discrete autoimmune entity within the "statin-induced myopathy spectrum". |journal=Autoimmunity Reviews |date=October 2013 |volume=12 |issue=12 |pages=1177–71 |doi=10.1016/j.autrev.2013.07.001 |pmid=23851103 |pmc=4589155 |type=Review}}</ref><ref name="Selva2018"/> [[Immunohistochemistry test]]ing may demonstrate additional pathologic features of SAAM including the presence of [[endothelial]] cell [[membrane attack complex]] in non-necrotic muscle fibers and [[MHC class I]] expression.<ref name="Selva2018"/>
| | The diagnosis of statin-associated autoimmune myopathy is based on a combination of clinical features, laboratory findings, and muscle biopsy results. Key diagnostic criteria include: |
| | | * Persistent muscle weakness despite discontinuation of statin therapy. |
| [[Antibodies]] against HMG-CoA reductase occur in 94% of affected individuals.<ref name="Thompson2016"/> These antibodies have been known to also occur in people who have never been exposed to statin medications.<ref name="Mammen2016"/> These antibodies have not been found in people who take statin medications but have not developed myopathy; thus, the presence of anti-HMGCoA reductase antibodies in a person who has taken a statin and have myopathy strongly supports this diagnosis.<ref name="Mammen2016"/> CK levels increase to 10-100 times the normal limit (2000-20,000 IU/L) in more than 90% of cases.<ref name="Mammen2016"/><ref name="Selva2018">{{cite journal |last1=Selva-O'Callaghan |first1=A |last2=Alvarado-Cardenas |first2=M |last3=Pinal-Fernández |first3=I |last4=Trallero-Araguás |first4=E |last5=Milisenda |first5=JC |last6=Martínez |first6=MA |last7=Marín |first7=A |last8=Labrador-Horrillo |first8=M |last9=Juárez |first9=C |last10=Grau-Junyent |first10=JM |title=Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations. |journal=Expert Review of Clinical Immunology |date=March 2018 |volume=14 |issue=3 |pages=215-24 |doi=10.1080/1744666X.2018.1440206 |pmid=29473763|pmc=6019601|type=Review}}</ref> [[Electromyography]] (EMG) demonstrates a myopathic pattern of findings.<ref name="Selva2018"/> [[Edema|Swelling]] of the muscles may be seen on [[Magnetic resonance imaging|MRI imaging]].<ref name="Mammen2016"/>
| | * Elevated serum [[creatine kinase]] levels. |
| | | * Presence of [[anti-HMG-CoA reductase antibodies]] in the blood. |
| | * Muscle biopsy showing necrotizing myopathy with minimal inflammation. |
| ==Treatment== | | ==Treatment== |
| SAAM is treated by stopping the offending statin medication and taking [[Immunosuppression|immunosuppressive medication]]s.<ref name="Hamann2013"/> In rare cases, affected people have had spontaneous improvement with stopping the implicated statin alone.<ref name="Mammen2016"/> However, this is typically not sufficient and immunosuppressive medication is needed in most cases.<ref name="Selva2018"/>
| | The primary treatment for statin-associated autoimmune myopathy involves discontinuation of the offending statin medication. In addition, immunosuppressive therapy is often required to control the autoimmune process. Commonly used immunosuppressive agents include [[corticosteroids]], [[methotrexate]], and [[azathioprine]]. In some cases, more aggressive treatments such as [[intravenous immunoglobulin]] (IVIG) or [[rituximab]] may be necessary. |
| | |
| [[Corticosteroid]]s are considered first-line treatment. [[Prednisone]] dosed at 1 milligram/kilogram of bodyweight daily is generally recommended.<ref name="Mammen2016"/> Corticosteroid therapy alone may be reasonable in cases of mild muscular weakness, but otherwise the addition of other immunosuppressive medications such as [[methotrexate]], [[azathioprine]], or [[mycophenolate]] is typical at the start of treatment.<ref name="Mammen2016"/> For severe cases unresponsive to this combination after 8-12 weeks, the addition of another medication (triple therapy) such as [[intravenous immunoglobulin]] or [[rituximab]] is recommended.<ref name="Mammen2016"/> Intravenous immunoglobulin has been successfully used as first-line treatment in selected individuals (e.g., people with [[diabetes mellitus]] who wish to avoid corticosteroid therapy).<ref name="Mammen2016"/>
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| ==Prognosis== | | ==Prognosis== |
| People affected by SAAM often regain complete muscle strength with proper treatment.<ref name="Mammen2016"/> This can occur even with persistently elevated [[creatine kinase]] (CK) levels.<ref name="Mammen2016"/> Conversely, some people with SAAM do not regain full muscle strength despite normalization of their CK levels.<ref name="Mammen2016"/> It is recommended that immunosuppressive medications be tapered once strength recovers.<ref name="Mammen2016"/> Relapse remains possible when these medications are tapered and some people do require long-term immunosuppression.<ref name="Mammen2016"/> If an affected person is inadequately treated for a long period of time, they are more likely to experience permanent muscle damage and weakness due to replacement of some muscle with [[Adipose tissue|fatty tissue]], which can be seen on MRI.<ref name="Mammen2016"/>
| | The prognosis for patients with statin-associated autoimmune myopathy varies. Some individuals may experience significant improvement in muscle strength and function with appropriate treatment, while others may have persistent weakness. Early recognition and treatment are crucial for improving outcomes. |
| | | ==Related pages== |
| ==References== | | * [[Statin]] |
| {{reflist}}
| | * [[Autoimmune disease]] |
| | | * [[Myopathy]] |
| ==External links==
| | * [[HMG-CoA reductase]] |
| [[Category:C-Class medicine articles]] | | [[Category:Autoimmune diseases]] |
| [[Category:Medication side effects]] | | [[Category:Muscular disorders]] |
| [[Category:Rheumatology]] | |
| [[Category:Statins]] | | [[Category:Statins]] |
| {{dictionary-stub1}}
| |
A rare autoimmune condition associated with statin use
Statin-associated autoimmune myopathy (SAAM) is a rare autoimmune disease that occurs in some individuals who are treated with statins, a class of drugs commonly used to lower cholesterol levels in the blood. This condition is characterized by muscle weakness and elevated levels of creatine kinase (CK) in the blood, indicating muscle damage.
Pathophysiology[edit]
Statins are known to inhibit the enzyme HMG-CoA reductase, which plays a crucial role in the mevalonate pathway of cholesterol synthesis. In some individuals, the use of statins can trigger an autoimmune response against HMG-CoA reductase itself, leading to muscle inflammation and damage. This autoimmune response is mediated by autoantibodies that target the enzyme, resulting in muscle weakness and myopathy.
Clinical Presentation[edit]
Patients with statin-associated autoimmune myopathy typically present with progressive muscle weakness, particularly in the proximal muscles such as those of the shoulders and hips. This weakness can lead to difficulties in performing everyday activities such as climbing stairs, lifting objects, or rising from a seated position. Muscle pain may also be present, although it is not as prominent as the weakness.
Diagnosis[edit]
The diagnosis of statin-associated autoimmune myopathy is based on a combination of clinical features, laboratory findings, and muscle biopsy results. Key diagnostic criteria include:
Treatment[edit]
The primary treatment for statin-associated autoimmune myopathy involves discontinuation of the offending statin medication. In addition, immunosuppressive therapy is often required to control the autoimmune process. Commonly used immunosuppressive agents include corticosteroids, methotrexate, and azathioprine. In some cases, more aggressive treatments such as intravenous immunoglobulin (IVIG) or rituximab may be necessary.
Prognosis[edit]
The prognosis for patients with statin-associated autoimmune myopathy varies. Some individuals may experience significant improvement in muscle strength and function with appropriate treatment, while others may have persistent weakness. Early recognition and treatment are crucial for improving outcomes.
Related pages[edit]
