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==Overview==
==Overview==
The underlying pathophysiology of polymyalgia rheumatica (PMR) remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with infections such as [[parainfluenza virus type 1]], [[mycoplasma pneumoniae]], [[chlamydia pneumoniae]], and [[parvovirus B19]]. In addition, histological exam of synovial biopsies of affected individuals revealed mild synovitis with predominance of [[CD4 T cells]] and [[macrophages]].
Polymyalgia rheumatica (PMR) is a chronic [[Inflammation|inflammatory]] disease of the [[articular]] and periarticular structures of the [[cervical]] region, [[Pectoral girdle|shoulder girdle]] and [[Hip (anatomy)|hip girdle]]. The underlying pathophysiology of PMR remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with [[Infection|infections]] such as [[parainfluenza virus type 1]], [[mycoplasma pneumoniae]], [[chlamydia pneumoniae]], and [[parvovirus B19]]. In addition, histological examinations of [[synovial]] [[Biopsy|biopsies]] of affected individuals reveal mild [[synovitis]] with predominance of [[CD4 T cells]] and [[macrophages]]. Although [[myalgia]] is a symptom of PMR, there is no [[inflammation]] of the [[muscle]]s.
 
==Pathophysiology==
 
=== Pathogenesis ===
* PMR is a chronic [[Inflammation|inflammatory]] disease of the [[articular]] and periarticular structures of the [[cervical]] region, [[shoulder girdle]] and [[hip girdle]]. 
* The cause of PMR remains unknown; however, there is evidence in the literature of possible involvement of [[Genetics|genetic]] and environmental factors.<ref name="pmid23051717">{{cite journal| author=Kermani TA, Warrington KJ| title=Polymyalgia rheumatica. | journal=Lancet | year= 2013 | volume= 381 | issue= 9860 | pages= 63-72 | pmid=23051717 | doi=10.1016/S0140-6736(12)60680-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23051717  }} </ref>
* This hypothesis is supported by the seasonal and geographical variations of the prevalence of PMR. In fact, the prevalence of PMR is the highest among patients from northern European descent and Scandinavian countries, which suggests a [[Genetics|genetic]] and/or environmental role in the [[pathophysiology]] of PMR.<ref name="pmid16414971">{{cite journal| author=Smeeth L, Cook C, Hall AJ| title=Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. | journal=Ann Rheum Dis | year= 2006 | volume= 65 | issue= 8 | pages= 1093-8 | pmid=16414971 | doi=10.1136/ard.2005.046912 | pmc=PMC1798240 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16414971  }} </ref><ref name="pmid19026700">{{cite journal| author=Alvarez-Rodriguez L, Carrasco-Marin E, Lopez-Hoyos M, Mata C, Fernandez-Prieto L, Ruiz-Soto M et al.| title=Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 genotype with polymyalgia rheumatica. | journal=Hum Immunol | year= 2009 | volume= 70 | issue= 1 | pages= 49-54 | pmid=19026700 | doi=10.1016/j.humimm.2008.10.011 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19026700  }} </ref><ref name="pmid2383076">{{cite journal| author=Cimmino MA, Caporali R, Montecucco CM, Rovida S, Baratelli E, Broggini M| title=A seasonal pattern in the onset of polymyalgia rheumatica. | journal=Ann Rheum Dis | year= 1990 | volume= 49 | issue= 7 | pages= 521-3 | pmid=2383076 | doi= | pmc=PMC1004141 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2383076  }} </ref>
*  Several [[Gene|genes]] have been reported to be involved in PMR, such as:<ref name="pmid8670595">{{cite journal| author=Haworth S, Ridgeway J, Stewart I, Dyer PA, Pepper L, Ollier W| title=Polymyalgia rheumatica is associated with both HLA-DRB1*0401 and DRB1*0404. | journal=Br J Rheumatol | year= 1996 | volume= 35 | issue= 7 | pages= 632-5 | pmid=8670595 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8670595  }} </ref><ref name="pmid8147928">{{cite journal| author=Weyand CM, Hunder NN, Hicok KC, Hunder GG, Goronzy JJ| title=HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis. | journal=Arthritis Rheum | year= 1994 | volume= 37 | issue= 4 | pages= 514-20 | pmid=8147928 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8147928  }} </ref><ref name="pmid16583473">{{cite journal| author=Boiardi L, Casali B, Farnetti E, Pipitone N, Nicoli D, Cantini F et al.| title=Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica. | journal=J Rheumatol | year= 2006 | volume= 33 | issue= 4 | pages= 703-8 | pmid=16583473 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16583473  }} </ref><ref name="pmid19026700">{{cite journal| author=Alvarez-Rodriguez L, Carrasco-Marin E, Lopez-Hoyos M, Mata C, Fernandez-Prieto L, Ruiz-Soto M et al.| title=Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 genotype with polymyalgia rheumatica. | journal=Hum Immunol | year= 2009 | volume= 70 | issue= 1 | pages= 49-54 | pmid=19026700 | doi=10.1016/j.humimm.2008.10.011 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19026700  }} </ref><ref name="pmid10943865">{{cite journal| author=Mattey DL, Hajeer AH, Dababneh A, Thomson W, González-Gay MA, García-Porrúa C et al.| title=Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms. | journal=Arthritis Rheum | year= 2000 | volume= 43 | issue= 8 | pages= 1749-55 | pmid=10943865 | doi=10.1002/1529-0131(200008)43:8<1749::AID-ANR11>3.0.CO;2-K | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10943865  }} </ref>
** [[HLA DRB1]]
** [[Interleukin 6]]
** [[Interleukin 1]] receptor antagonist
** [[Tumor necrosis factor]] 3b (TNFb3)
 
* Moreover, the association between PMR and [[Infection|infections]] is another hypothesis for the development of PMR through [[Virus|viral]] stimulation of the [[immune system]]. This hypothesis is supported by the highest incidence of PMR in the time of some [[infection]] epidemics.  Some of the [[Infection|infections]] that have been linked to PMR are:<ref name="pmid9972970">{{cite journal| author=Duhaut P, Bosshard S, Calvet A, Pinede L, Demolombe-Rague S, Dumontet C et al.| title=Giant cell arteritis, polymyalgia rheumatica, and viral hypotheses: a multicenter, prospective case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes. | journal=J Rheumatol | year= 1999 | volume= 26 | issue= 2 | pages= 361-9 | pmid=9972970 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9972970  }} </ref><ref name="pmid8838518">{{cite journal| author=Elling P, Olsson AT, Elling H| title=Synchronous variations of the incidence of temporal arteritis and polymyalgia rheumatica in different regions of Denmark; association with epidemics of Mycoplasma pneumoniae infection. | journal=J Rheumatol | year= 1996 | volume= 23 | issue= 1 | pages= 112-9 | pmid=8838518 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8838518  }} </ref>
** [[Parainfluenza virus type 1]]
** [[Mycoplasma pneumoniae]]
** [[Chlamydia pneumoniae]]
** [[Parvovirus B19]]
 
* In addition to the previous hypotheses, it has been postulated that PMR can be explained by an age related dysregulation in the [[hypothalamus]], [[pituitary gland]] and [[gonads]].  This disturbance leads to [[adrenal insufficiency]] and decrement in [[dehydroepiandrosterone]] or [[androstenedione]].<ref name="pmid16821261">{{cite journal| author=Straub RH, Cutolo M| title=Further evidence for insufficient hypothalamic-pituitary-glandular axes in polymyalgia rheumatica. | journal=J Rheumatol | year= 2006 | volume= 33 | issue= 7 | pages= 1219-23 | pmid=16821261 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16821261  }} </ref>
 
* Imaging studies such as [[ultrasound]] and [[MRI]] reveal [[inflammation]] in the [[articular]] and periarticular regions. The examination of histopathological specimens demonstrates mild [[synovitis]] with a predominance of [[T helper cells]] and [[macrophages]].<ref name="pmid8670331">{{cite journal| author=Meliconi R, Pulsatelli L, Uguccioni M, Salvarani C, Macchioni P, Melchiorri C et al.| title=Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment. | journal=Arthritis Rheum | year= 1996 | volume= 39 | issue= 7 | pages= 1199-207 | pmid=8670331 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8670331  }} </ref>
 
== Associated conditions ==
* Polymyalgia rheumatica may be associated with the following conditions:<ref name="pmid24364483">{{cite journal| author=Caylor TL, Perkins A| title=Recognition and management of polymyalgia rheumatica and giant cell arteritis. | journal=Am Fam Physician | year= 2013 | volume= 88 | issue= 10 | pages= 676-84 | pmid=24364483 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24364483  }}</ref><ref name="SalvaraniCantini2008">{{cite journal|last1=Salvarani|first1=Carlo|last2=Cantini|first2=Fabrizio|last3=Hunder|first3=Gene G|title=Polymyalgia rheumatica and giant-cell arteritis|journal=The Lancet|volume=372|issue=9634|year=2008|pages=234–245|issn=01406736|doi=10.1016/S0140-6736(08)61077-6}}</ref>
** [[Temporal arteritis|Giant cell arteritis]] ([[temporal arteritis]])
** [[Systemic lupus erythematosus]]
** [[Rheumatoid arthritis]]


== Microscopic Pathology ==
* In cases the polymyalgia rheumatica associated with [[Temporal arteritis|giant cell arteritis]], [[microscopic]] histopathological analysis will show the following findings of [[arteritis]]:<ref name="pmid7728064">{{cite journal| author=Pountain G, Hazleman B| title=ABC of rheumatology. Polymyalgia rheumatica and giant cell arteritis. | journal=BMJ | year= 1995 | volume= 310 | issue= 6986 | pages= 1057-9 | pmid=7728064 | doi= | pmc=2549437 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7728064  }}</ref><ref name="pmid10817557">{{cite journal| author=Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JJ| title=Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity. | journal=Arthritis Rheum | year= 2000 | volume= 43 | issue= 5 | pages= 1041-8 | pmid=10817557 | doi=10.1002/1529-0131(200005)43:5<1041::AID-ANR12>3.0.CO;2-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10817557  }}</ref><ref name="pmid28275606">{{cite journal| author=Wang AL, Raven ML, Surapaneni K, Albert DM| title=Studies on the Histopathology of Temporal Arteritis. | journal=Ocul Oncol Pathol | year= 2017 | volume= 3 | issue= 1 | pages= 60-65 | pmid=28275606 | doi=10.1159/000449466 | pmc=5318845 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28275606  }}</ref>
**Skip lesions and normal intervening segments
**Intimal thickening, with prominent [[cellular infiltration]]
**[[Lymphocyte|Lymphocytes]] in the internal or external elastic lamina or [[adventitia]]
**Areas of [[necrosis]] may be present in the [[Artery|arterial]] wall
**[[Granuloma|Granulomas]] containing [[Multinucleate|multinucleated]] [[Histiocyte|histiocytic]] and foreign body [[Macrophage|giant cells]], [[T helper cell|helper T-cell]] [[Lymphocyte|lymphocytes]], [[Plasma cell|plasma cells]], and [[Fibroblast|fibroblasts]]<ref name="pmid23523078">{{cite journal| author=Liozon E, Ly KH, Robert PY| title=[Ocular complications of giant cell arteritis]. | journal=Rev Med Interne | year= 2013 | volume= 34 | issue= 7 | pages= 421-30 | pmid=23523078 | doi=10.1016/j.revmed.2013.02.030 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23523078  }}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 23:47, 29 July 2020


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Overview

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle. The underlying pathophysiology of PMR remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with infections such as parainfluenza virus type 1, mycoplasma pneumoniae, chlamydia pneumoniae, and parvovirus B19. In addition, histological examinations of synovial biopsies of affected individuals reveal mild synovitis with predominance of CD4 T cells and macrophages. Although myalgia is a symptom of PMR, there is no inflammation of the muscles.

Pathophysiology

Pathogenesis

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References

  1. ↑ Kermani TA, Warrington KJ (2013). "Polymyalgia rheumatica". Lancet. 381 (9860): 63–72. doi:10.1016/S0140-6736(12)60680-1. PMID 23051717.
  2. ↑ Smeeth L, Cook C, Hall AJ (2006). "Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001". Ann Rheum Dis. 65 (8): 1093–8. doi:10.1136/ard.2005.046912. PMC 1798240. PMID 16414971.
  3. ↑ 3.0 3.1 Alvarez-Rodriguez L, Carrasco-Marin E, Lopez-Hoyos M, Mata C, Fernandez-Prieto L, Ruiz-Soto M; et al. (2009). "Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 genotype with polymyalgia rheumatica". Hum Immunol. 70 (1): 49–54. doi:10.1016/j.humimm.2008.10.011. PMID 19026700.
  4. ↑ Cimmino MA, Caporali R, Montecucco CM, Rovida S, Baratelli E, Broggini M (1990). "A seasonal pattern in the onset of polymyalgia rheumatica". Ann Rheum Dis. 49 (7): 521–3. PMC 1004141. PMID 2383076.
  5. ↑ Haworth S, Ridgeway J, Stewart I, Dyer PA, Pepper L, Ollier W (1996). "Polymyalgia rheumatica is associated with both HLA-DRB1*0401 and DRB1*0404". Br J Rheumatol. 35 (7): 632–5. PMID 8670595.
  6. ↑ Weyand CM, Hunder NN, Hicok KC, Hunder GG, Goronzy JJ (1994). "HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis". Arthritis Rheum. 37 (4): 514–20. PMID 8147928.
  7. ↑ Boiardi L, Casali B, Farnetti E, Pipitone N, Nicoli D, Cantini F; et al. (2006). "Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica". J Rheumatol. 33 (4): 703–8. PMID 16583473.
  8. ↑ Mattey DL, Hajeer AH, Dababneh A, Thomson W, González-Gay MA, García-Porrúa C; et al. (2000). "Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms". Arthritis Rheum. 43 (8): 1749–55. doi:10.1002/1529-0131(200008)43:8<1749::AID-ANR11>3.0.CO;2-K. PMID 10943865.
  9. ↑ Duhaut P, Bosshard S, Calvet A, Pinede L, Demolombe-Rague S, Dumontet C; et al. (1999). "Giant cell arteritis, polymyalgia rheumatica, and viral hypotheses: a multicenter, prospective case-control study. Groupe de Recherche sur l'Artérite à Cellules Géantes". J Rheumatol. 26 (2): 361–9. PMID 9972970.
  10. ↑ Elling P, Olsson AT, Elling H (1996). "Synchronous variations of the incidence of temporal arteritis and polymyalgia rheumatica in different regions of Denmark; association with epidemics of Mycoplasma pneumoniae infection". J Rheumatol. 23 (1): 112–9. PMID 8838518.
  11. ↑ Straub RH, Cutolo M (2006). "Further evidence for insufficient hypothalamic-pituitary-glandular axes in polymyalgia rheumatica". J Rheumatol. 33 (7): 1219–23. PMID 16821261.
  12. ↑ Meliconi R, Pulsatelli L, Uguccioni M, Salvarani C, Macchioni P, Melchiorri C; et al. (1996). "Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment". Arthritis Rheum. 39 (7): 1199–207. PMID 8670331.
  13. ↑ Caylor TL, Perkins A (2013). "Recognition and management of polymyalgia rheumatica and giant cell arteritis". Am Fam Physician. 88 (10): 676–84. PMID 24364483.
  14. ↑ Salvarani, Carlo; Cantini, Fabrizio; Hunder, Gene G (2008). "Polymyalgia rheumatica and giant-cell arteritis". The Lancet. 372 (9634): 234–245. doi:10.1016/S0140-6736(08)61077-6. ISSN 0140-6736.
  15. ↑ Pountain G, Hazleman B (1995). "ABC of rheumatology. Polymyalgia rheumatica and giant cell arteritis". BMJ. 310 (6986): 1057–9. PMC 2549437. PMID 7728064.
  16. ↑ Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JJ (2000). "Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity". Arthritis Rheum. 43 (5): 1041–8. doi:10.1002/1529-0131(200005)43:5<1041::AID-ANR12>3.0.CO;2-7. PMID 10817557.
  17. ↑ Wang AL, Raven ML, Surapaneni K, Albert DM (2017). "Studies on the Histopathology of Temporal Arteritis". Ocul Oncol Pathol. 3 (1): 60–65. doi:10.1159/000449466. PMC 5318845. PMID 28275606.
  18. ↑ Liozon E, Ly KH, Robert PY (2013). "[Ocular complications of giant cell arteritis]". Rev Med Interne. 34 (7): 421–30. doi:10.1016/j.revmed.2013.02.030. PMID 23523078.
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