335:(CK) levels. Conversely, some people with SAAM do not regain full muscle strength despite the normalization of their CK levels. Longitudinal analysis of a patient cohort revealed that the majority of patients (85%) over 60 years old recovered full strength within four years, compared to less than half of patients below 52 years old, indicating that age during disease onset may be an important prognostic determinant. Once strength recovers, immunosuppressive medications should be tapered. Relapse remains possible during tapering efforts, and some people require long-term immunosuppression. An affected person is more likely to experience permanent muscle damage if they do not receive adequate treatment for a long time. Muscle weakness occurs due to the replacement of some muscle with
221:
262:
against HMG-CoA reductase occur in 94% of affected individuals. These antibodies are known to also occur in people who do not take statin medications. Conversely, these antibodies are absent in people who take statin medications but do not have myopathy. Thus, the presence of anti-HMG CoA reductase
207:
levels in the blood. However, by doing this, they also increase the production of the HMG-CoA reductase protein. SAAM hypothetically triggers this increase in the production of HMG-CoA reductase and associated abnormal processing of this protein in genetically susceptible individuals. This abnormal
182:
A differentiating feature between this and more benign statin side effects is SAAM typically has a late onset. While muscle pain (myalgia) is seen in 9-20% of patients treated with statins, it typically occurs in the first month of treatment. SAAM has a later onset, occurring years after
208:
processing theoretically triggers the generation of antibodies targeting the HMG-CoA reductase protein resulting in SAAM. 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
178:
and rash may be present. In people affected by SAAM, the median duration of statin therapy was 38 months before the onset of muscular symptoms. SAAM may affect people after long-term statin use even if they had no previous muscular side effects.
318:
are recommended as add-on therapy in such cases. Intravenous immunoglobulin is an appropriate first-line therapy in select individuals. Suitable candidates for first-line intravenous immunoglobulin include people who have
41:
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
199:. There are likely 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. Statins inhibit
297:
dosed at 1 milligram/kilogram of body weight daily is generally recommended. Corticosteroid therapy alone may be reasonable in cases of mild muscular weakness. More severe cases require the use of combined
766:
Selva-O'Callaghan, A; Alvarado-Cardenas, M; Pinal-FernĂĄndez, I; Trallero-AraguĂĄs, E; Milisenda, JC; MartĂnez, MA; MarĂn, A; Labrador-Horrillo, M; JuĂĄrez, C; Grau-Junyent, JM (March 2018).
263:
antibodies in someone who uses a statin and has myopathy strongly supports the diagnosis. CK levels increase to 10-100 times above normal (2000â20,000 IU/L) in more than 90% of cases.
111:
medications. However, there are cases of SAAM in patients who have not taken statin medication, and this can be explained by the exposure to natural sources of statin such as
689:
287:. In rare cases, affected people spontaneously improve after just stopping the implicated statin. However, most cases mandate the use of immunosuppressive medication.
412:"Clinical characteristics of anti-3-hydroxy-3-methylglutaryl coenzyme a reductase antibodies in Chinese patients with idiopathic inflammatory myopathies"
817:"More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglu- taryl-coenzyme A reductase-associated autoimmune myopathy"
115:, which is statin rich. This theory is supported by the higher prevalence of statin-naive SAAM patients in Asian cohorts, who have statin-rich diets.
228:
The development of necrotizing myopathy after statin exposure is insufficient to make the diagnosis. Testing must first exclude other causes of
872:
548:
Christopher-Stine, L; Basharat, P (April 2017). "Statin-associated immune-mediated myopathy: biology and clinical implications".
155:
Severe weakness of the proximal muscles (shoulders, upper arms, thighs) on both sides of the body, very high blood levels of the
640:
Selva-O'Callaghan A, Alvarado-Cardenas M, Pinal-FernĂĄndez I, Trallero-AraguĂĄs E, Milisenda JC, MartĂnez MĂ; et al. (2018).
191:
It is unclear precisely how statins lead to statin-associated autoimmune myopathy. The disorder is positively associated with
76:
315:
272:
710:"Statin-induced necrotizing myositis - a discrete autoimmune entity within the "statin-induced myopathy spectrum""
241:
144:
220:
118:
The exact cause is unclear. A combination of consistent findings on physical examination, the presence of anti
331:
Proper treatment of SAAM often results in full recovery. Recovery can occur even with persistently elevated
249:
147:
out of every 100,000 statin-treated individuals. It appears to be more common in people over the age of 50.
877:
683:
423:
310:
with corticosteroids. Severe cases of SAAM may fail to respond to 8â12 weeks of combination therapy.
183:
uncomplicated statin use. In some cases even after statins have been discontinued for several years.
573:
59:
17:
212:
that the immune system is not tolerant to resulting in the production of antibodies against it.
848:
797:
739:
671:
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614:
565:
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244:
may demonstrate additional pathologic features of SAAM. Such findings include the presence of
200:
137:
119:
47:
768:"Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations"
642:"Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations"
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838:
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843:
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446:
411:
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medication are the hallmarks of SAAM. Other forms of statin associated muscle damage (
112:
72:
136:
Treatment involves stopping the associated statin medication and taking medication to
866:
307:
233:
130:
104:
577:
303:
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52:
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166:, and persistent symptoms and CK elevation despite stopping the offending
592:
240:
with muscle fiber regeneration and typically has few inflammatory cells.
237:
229:
192:
171:
126:
100:
283:
SAAM is treated by stopping the offending statin medication and taking
209:
510:
Mammen, AL (February 2016). "Statin-Associated
Autoimmune Myopathy".
267:(EMG) typically demonstrates a myopathic pattern of findings. Muscle
196:
167:
156:
108:
80:
268:
219:
593:"Anti-HMGCR Myopathy: A Rare and Serious Side Effect of Statins"
708:
Hamann, PD; Cooper, RG; McHugh, NJ; Chinoy, H (October 2013).
99:, also known as anti-HMGCR myopathy, is a very rare form of
815:
Tiniakou, E; Pinal-Fernandez, I; Lloyd, TE (January 2017).
174:) usually resolve after stopping the involved statin. Mild
369:
Thompson, PD; Panza, G; Zaleski, A; Taylor, B (May 2016).
597:
The
Journal of the American Board of Family Medicine
224:
Diagnostic algorithm for statin-associated myopathy.
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68:
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37:
32:
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375:Journal of the American College of Cardiology
323:or who wish to avoid corticosteroid therapy.
8:
703:
701:
699:
688:: CS1 maint: multiple names: authors list (
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481:
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97:Statin-associated autoimmune myopathy (SAAM)
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29:
842:
832:
791:
733:
665:
608:
445:
435:
386:
348:
681:
236:consistent with SAAM will demonstrate
293:are considered first-line treatment.
33:Statin-associated Autoimmune Myopathy
7:
772:Expert Review of Clinical Immunology
162:(CK) being released by broken down
129:, evidence of muscle breakdown, and
591:Irvine, Nathaniel J. (2020-09-01).
252:in non-necrotic muscle fibers and
25:
18:Statin-associated muscle symptoms
371:"Statin-Associated Side Effects"
203:activity and consequently lower
512:New England Journal of Medicine
410:Ge, Y; Peng, Q (October 2015).
79:, withdrawal of the implicated
1:
784:10.1080/1744666X.2018.1440206
658:10.1080/1744666X.2018.1440206
550:Current Opinion in Lipidology
285:immunosuppressive medications
77:immunosuppressive medications
726:10.1016/j.autrev.2013.07.001
610:10.3122/jabfm.2020.05.190450
562:10.1097/MOL.0000000000000399
437:10.1371/journal.pone.0141616
242:Immunohistochemistry testing
232:and necrotizing myopathy. A
834:10.1093/rheumatology/kew470
899:
388:10.1016/j.jacc.2016.02.071
316:intravenous immunoglobulin
138:suppress the immune system
873:Medication side effects
646:Expert Rev Clin Immunol
250:membrane attack complex
225:
524:10.1056/NEJMra1515161
223:
143:SAAM is estimated to
714:Autoimmunity Reviews
428:2015PLoSO..1041616G
195:and the DRB1*11:01
145:occur in 2-3 people
107:in people who take
226:
151:Signs and symptoms
381:(20): 2395â2410.
321:diabetes mellitus
238:muscle cell death
201:HMG-CoA reductase
125:in a person with
120:HMG-CoA reductase
94:
93:
27:Medical condition
16:(Redirected from
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857:
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422:(10): e0141616.
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265:Electromyography
30:
21:
898:
897:
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863:
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720:(12): 1177â71.
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333:creatine kinase
329:
291:Corticosteroids
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271:may be seen on
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164:skeletal muscle
160:creatine kinase
153:
133:diagnose SAAM.
73:Corticosteroids
64:Muscle weakness
28:
23:
22:
15:
12:
11:
5:
896:
894:
886:
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827:(5): 787â794.
807:
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652:(3): 215â224.
632:
603:(5): 785â788.
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113:red yeast rice
103:caused by the
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778:(3): 215â24.
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556:(2): 186â92.
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308:mycophenolate
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234:muscle biopsy
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131:muscle biopsy
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105:immune system
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101:muscle damage
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878:Rheumatology
824:
821:Rheumatology
820:
810:
775:
771:
717:
713:
684:cite journal
649:
645:
635:
600:
596:
586:
553:
549:
518:(7): 664â9.
515:
511:
419:
415:
405:
378:
374:
337:fatty tissue
330:
304:azathioprine
300:methotrexate
289:
282:
258:
256:expression.
227:
190:
187:Pathogenesis
181:
154:
142:
135:
117:
96:
95:
53:Rheumatology
273:MRI imaging
254:MHC class I
246:endothelial
205:cholesterol
38:Other names
867:Categories
774:(Review).
716:(Review).
552:(Review).
514:(Review).
377:(Review).
343:References
295:Prednisone
260:Antibodies
176:joint pain
123:antibodies
619:1557-2625
327:Prognosis
312:Rituximab
279:Treatment
216:Diagnosis
87:Frequency
69:Treatment
48:Specialty
853:28096458
802:29473763
744:23851103
676:29473763
627:32989074
578:19330288
570:28207435
532:26886523
456:26509687
416:PLOS ONE
397:27199064
269:swelling
230:myositis
210:antigens
193:HLA-DR11
172:myopathy
127:myopathy
60:Symptoms
42:myopathy
883:Statins
844:5850825
793:6019601
735:4589155
667:6019601
447:4624805
424:Bibcode
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841:
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790:
742:
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197:allele
168:statin
157:enzyme
109:statin
81:statin
574:S2CID
306:, or
248:cell
849:PMID
798:PMID
740:PMID
690:link
672:PMID
623:PMID
615:ISSN
566:PMID
528:PMID
452:PMID
393:PMID
90:Rare
839:PMC
829:doi
788:PMC
780:doi
730:PMC
722:doi
662:PMC
654:doi
605:doi
558:doi
520:doi
516:374
442:PMC
432:doi
383:doi
314:or
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