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Spondyloarthropathy, susceptibility to, 1(SPDA1)

MedGen UID:
400145
Concept ID:
C1862852
Finding
Synonyms: Ankylosing spondylitis 1; ANKYLOSING SPONDYLITIS, SUSCEPTIBILITY TO; ANKYLOSING SPONDYLITIS, SUSCEPTIBILITY TO, 1; SPDA1
 
Gene (location): HLA-B (6p21.33)
 
Monarch Initiative: MONDO:0007126
OMIM®: 106300

Definition

Spondyloarthropathy (SpA), one of the commonest chronic rheumatic diseases, includes a spectrum of related disorders comprising the prototype ankylosing spondylitis (AS), a subset of psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthropathy (Miceli-Richard et al., 2004). These phenotypes are difficult to differentiate because they may occur simultaneously or sequentially in the same patient. Studies have suggested that a predominant shared component, including HLA-B27, predisposes to all phenotypic subsets, and that these subsets should be considered as various phenotypic expressions of the same disease (Said-Nahal et al., 2000, Said-Nahal et al., 2001). Braun and Sieper (2007) provided a detailed review of ankylosing spondylitis, including clinical features, pathogenesis, and management. Genetic Heterogeneity of Susceptibility to Spondyloarthropathy Additional susceptibility loci for spondyloarthropathy have been identified on chromosome 9q31-q34 (SPDA2; 183840) and chromosome 2q36 (SPDA3; 613238). [from OMIM]

Additional description

From MedlinePlus Genetics
Ankylosing spondylitis is a form of painful, ongoing joint inflammation (chronic inflammatory arthritis) that primarily affects the spine.  Early symptoms of ankylosing spondylitis typically begin between the ages of 15 and 30. Most commonly, affected individuals first experience chronic back pain and stiffness. This pain worsens with rest or inactivity, and tends to be relieved with physical activity or exercise.

Pain in ankylosing spondylitis results from inflammation of the joints between the pelvic bones (the ilia) and the base of the spine (the sacrum). These joints are called sacroiliac joints, and inflammation of these joints is known as sacroiliitis. The inflammation gradually spreads to the joints between the vertebrae, eventually involving the whole spine, causing a condition called spondylitis. Over time, back movement gradually becomes limited as the bones of the spine (vertebrae) fuse together. This progressive bony fusion is called ankylosis. These fused bones are prone to fracture.

Ankylosing spondylitis can involve other joints as well, including the shoulders, hips, and, less often, the knees. As the disease progresses, it can affect the joints between the spine and ribs, restricting movement of the chest and making it difficult to breathe deeply. 

Ankylosing spondylitis affects the eyes in more than 30 percent of cases, leading to episodes of eye inflammation called acute iritis. Acute iritis typically affects one eye at a time and causes eye pain and increased sensitivity to light (photophobia). Rarely, ankylosing spondylitis can also cause serious complications involving the heart, lungs, and nervous system. Six to 10 percent of people with ankylosing spondylitis have additional inflammatory disorders such as psoriasis, which affects the skin, or ulcerative colitis or Crohn's disease, which both affect the digestive tract.  https://medlineplus.gov/genetics/condition/ankylosing-spondylitis

Clinical features

From HPO
Back pain
MedGen UID:
2530
Concept ID:
C0004604
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the back.
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
Inflammation of the large intestine
MedGen UID:
662273
Concept ID:
C0578878
Disease or Syndrome
Inflammation, or an inflammatory state in the large intestine.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Osteoarthritis, hip
MedGen UID:
14530
Concept ID:
C0029410
Disease or Syndrome
Osteoarthritis of the hip joint.
Arthritis, sacroiliac
MedGen UID:
148186
Concept ID:
C0748473
Disease or Syndrome
Inflammation of the sacroiliac joint, generally accompanied by lower back pain.
Enthesitis
MedGen UID:
451081
Concept ID:
C1282952
Disease or Syndrome
Inflammation at the site of insertion of ligaments, tendons, and other fibrous structures into bone.
Oligoarthritis
MedGen UID:
856143
Concept ID:
C3892044
Disease or Syndrome
A type of arthritis that affects up to four joints in the first six months of disease.
Anterior uveitis
MedGen UID:
22595
Concept ID:
C0042165
Disease or Syndrome
Inflammation of the uveal tract in which the primary site of inflammation is the anterior chamber.
Rheumatoid factor positive
MedGen UID:
56226
Concept ID:
C0151379
Laboratory or Test Result
The presence in the serum of an autoantibody directed against the Fc portion of IgG.
Psoriasiform dermatitis
MedGen UID:
75508
Concept ID:
C0262985
Disease or Syndrome
A skin abnormality characterized by redness and irritation, with thick, red skin that displays flaky, silver-white patches (scales).

Professional guidelines

PubMed

Rosenbaum JT, Weisman MH, Hamilton H, Shafer C, Aslanyan E, Howard RA, Ogle K, Reveille JD, Winthrop KL, Choi D
J Rheumatol 2022 Feb;49(2):225-229. Epub 2021 Oct 1 doi: 10.3899/jrheum.210742. PMID: 34599048
Reveille JD
Clin Rheumatol 2015 Jun;34(6):1009-18. Epub 2015 May 5 doi: 10.1007/s10067-015-2949-3. PMID: 25939520Free PMC Article
Garcia-Valladares I, Cuchacovich R, Espinoza LR
Drug Des Devel Ther 2011 Jan 10;5:41-9. doi: 10.2147/DDDT.S10494. PMID: 21267358Free PMC Article

Recent clinical studies

Etiology

Haberman RH, MacFarlane KA, Catron S, Samuels J, Blank RB, Toprover M, Uddin Z, Hu J, Castillo R, Gong C, Qian K, Piguet V, Tausk F, Yeung J, Neimann AL, Gulliver W, Thiele RG, Merola JF, Ogdie A, Rahman P, Chakravarty SD, Eder L, Ritchlin CT, Scher JU
BMJ Open 2022 Dec 23;12(12):e063650. doi: 10.1136/bmjopen-2022-063650. PMID: 36564123Free PMC Article
Li Y, Guo J, Cao Z, Wu J
Front Immunol 2022;13:916645. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.916645. PMID: 35757704Free PMC Article
Tavasolian F, Inman RD
Autoimmun Rev 2021 Jun;20(6):102827. Epub 2021 Apr 20 doi: 10.1016/j.autrev.2021.102827. PMID: 33864943
O'Rielly DD, Rahman P
Best Pract Res Clin Rheumatol 2014 Oct;28(5):673-85. Epub 2014 Nov 22 doi: 10.1016/j.berh.2014.10.010. PMID: 25488777
Breban M, Miceli-Richard C, Zinovieva E, Monnet D, Said-Nahal R
Joint Bone Spine 2006 Jul;73(4):355-62. Epub 2006 Mar 20 doi: 10.1016/j.jbspin.2005.11.010. PMID: 16650794

Diagnosis

Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, Sartor RB, Haritunians T, McGovern DPB
Gastroenterology 2024 Jul;167(2):315-332. Epub 2024 Mar 13 doi: 10.1053/j.gastro.2024.02.026. PMID: 38490347Free PMC Article
Li Y, Guo J, Cao Z, Wu J
Front Immunol 2022;13:916645. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.916645. PMID: 35757704Free PMC Article
Charoenngam N
Int J Mol Sci 2021 Oct 1;22(19) doi: 10.3390/ijms221910659. PMID: 34639000Free PMC Article
Khazim K, Azulay EE, Kristal B, Cohen I
Immunol Rev 2018 Jan;281(1):40-56. doi: 10.1111/imr.12620. PMID: 29247999
Smith JA
Curr Allergy Asthma Rep 2015 Jan;15(1):489. doi: 10.1007/s11882-014-0489-6. PMID: 25447326

Therapy

Haberman RH, MacFarlane KA, Catron S, Samuels J, Blank RB, Toprover M, Uddin Z, Hu J, Castillo R, Gong C, Qian K, Piguet V, Tausk F, Yeung J, Neimann AL, Gulliver W, Thiele RG, Merola JF, Ogdie A, Rahman P, Chakravarty SD, Eder L, Ritchlin CT, Scher JU
BMJ Open 2022 Dec 23;12(12):e063650. doi: 10.1136/bmjopen-2022-063650. PMID: 36564123Free PMC Article
Li Y, Guo J, Cao Z, Wu J
Front Immunol 2022;13:916645. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.916645. PMID: 35757704Free PMC Article
Charoenngam N
Int J Mol Sci 2021 Oct 1;22(19) doi: 10.3390/ijms221910659. PMID: 34639000Free PMC Article
Khazim K, Azulay EE, Kristal B, Cohen I
Immunol Rev 2018 Jan;281(1):40-56. doi: 10.1111/imr.12620. PMID: 29247999
Keat A
Adv Exp Med Biol 1999;455:201-6. doi: 10.1007/978-1-4615-4857-7_29. PMID: 10599344

Prognosis

Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z
Front Immunol 2024;15:1417564. Epub 2024 Jul 4 doi: 10.3389/fimmu.2024.1417564. PMID: 39026678Free PMC Article
Shi C, Rattray M, Barton A, Bowes J, Orozco G
Rheumatology (Oxford) 2020 Nov 1;59(11):3137-3146. doi: 10.1093/rheumatology/keaa283. PMID: 32778885Free PMC Article
Zhang Z, Deng C, Ma X, Liu X
Clin Exp Rheumatol 2020 Sep-Oct;38(5):993-1000. Epub 2020 Jan 28 PMID: 31994481
Leccese P, Alpsoy E
Front Immunol 2019;10:1067. Epub 2019 May 10 doi: 10.3389/fimmu.2019.01067. PMID: 31134098Free PMC Article
Berthelot JM
Reumatismo 2003;55(1):6-15. doi: 10.4081/reumatismo.2003.6. PMID: 12649695

Clinical prediction guides

Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, Sartor RB, Haritunians T, McGovern DPB
Gastroenterology 2024 Jul;167(2):315-332. Epub 2024 Mar 13 doi: 10.1053/j.gastro.2024.02.026. PMID: 38490347Free PMC Article
Haberman RH, MacFarlane KA, Catron S, Samuels J, Blank RB, Toprover M, Uddin Z, Hu J, Castillo R, Gong C, Qian K, Piguet V, Tausk F, Yeung J, Neimann AL, Gulliver W, Thiele RG, Merola JF, Ogdie A, Rahman P, Chakravarty SD, Eder L, Ritchlin CT, Scher JU
BMJ Open 2022 Dec 23;12(12):e063650. doi: 10.1136/bmjopen-2022-063650. PMID: 36564123Free PMC Article
Li Y, Guo J, Cao Z, Wu J
Front Immunol 2022;13:916645. Epub 2022 Jun 10 doi: 10.3389/fimmu.2022.916645. PMID: 35757704Free PMC Article
Charoenngam N
Int J Mol Sci 2021 Oct 1;22(19) doi: 10.3390/ijms221910659. PMID: 34639000Free PMC Article
Shi C, Rattray M, Barton A, Bowes J, Orozco G
Rheumatology (Oxford) 2020 Nov 1;59(11):3137-3146. doi: 10.1093/rheumatology/keaa283. PMID: 32778885Free PMC Article

Recent systematic reviews

Gao M, Li T, Song Z, Wang X, Zhang X, Liu W
Biochem Genet 2022 Jun;60(3):1025-1038. Epub 2021 Nov 11 doi: 10.1007/s10528-021-10149-5. PMID: 34762200
Xia Y, Liang Y, Guo S, Yu JG, Tang MS, Xu PH, Qin FD, Wang GP
Postgrad Med J 2018 Sep;94(1115):508-516. Epub 2018 Oct 15 doi: 10.1136/postgradmedj-2018-135665. PMID: 30322951
Qian Y, Wang G, Xue F, Chen L, Wang Y, Tang L, Yang H
Inflamm Res 2017 Aug;66(8):653-661. Epub 2017 Apr 12 doi: 10.1007/s00011-017-1047-1. PMID: 28405734
Chen S, Li Y, Deng C, Li J, Wen X, Wu Z, Hu C, Zhang S, Li P, Zhang X, Zhang F, Li Y
Rheumatol Int 2016 Jan;36(1):33-44. Epub 2015 Aug 1 doi: 10.1007/s00296-015-3327-9. PMID: 26232179
Zhao S, Duffield SJ, Moots RJ, Goodson NJ
Rheumatology (Oxford) 2014 Sep;53(9):1595-603. Epub 2014 Apr 4 doi: 10.1093/rheumatology/keu042. PMID: 24706990

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