Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy 

  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Apr 16, 2012
 

Background

Ankylosing spondylitis (AS) is a chronic, multisystem inflammatory disorder primarily involving the sacroiliac (SI) joints and the axial skeleton. Other clinical manifestations include peripheral arthritis, enthesitis, and extra-articular organ involvement.[1, 2, 3, 4] It has been designated by various names, including rheumatoid spondylitis in the American literature, spondyloarthrite rhizomegalique in the French literature, and the eponyms Marie-Strümpell disease and von Bechterew disease.

AS is the prototype of the spondyloarthropathies, a family of related disorders that also includes reactive arthritis (ReA), psoriatic arthritis (PsA), spondyloarthropathy associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthropathy (USpA), and, possibly, Whipple disease and Behçet disease (see the image below). The spondyloarthropathies are linked by common genetics (the human leukocyte antigen [HLA] class-I gene HLA-B27) and a common pathology (enthesitis).

The family of spondyloarthropathies The family of spondyloarthropathies

AS is classified as a spondyloarthropathy. The disorder is often found in association with other spondyloarthropathies, including ReA, PsA, ulcerative colitis (UC), and Crohn disease. Patients often have a family history of either AS or another spondyloarthropathy.

The etiology of AS is not understood completely; however, a strong genetic predisposition exists.[5, 6] A direct relationship between AS and the HLA-B27 gene has been determined.[7, 8, 9, 10] The precise role of HLA-B27 in precipitating AS remains unknown; however, it is believed that HLA-B27 may resemble or act as a receptor for an inciting antigen, such as bacteria.

The diagnosis of AS is generally made by combining clinical criteria of inflammatory back pain and enthesitis or arthritis with radiological findings. Early diagnosis is important because early medical and physical therapy may improve functional outcome. As with any chronic disease, patient education is vital to familiarize the patient with the symptoms, course, and treatment of the disease. Treatment measures include pharmacologic, physical therapy, and surgical.

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Pathophysiology

The spondyloarthropathies are chronic inflammatory diseases that most commonly involve the SI joints and the axial skeleton, with hip and shoulder joints less frequently affected. Peripheral joints and entheses and certain extra-articular organs, including the eyes, skin, and cardiovascular system, may be involved to a lesser degree.

The primary pathology of the spondyloarthropathies is enthesitis with chronic inflammation, including CD4+ and CD8+ T lymphocytes and macrophages. Cytokines, particularly tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), are also important in the inflammatory process by leading to fibrosis and ossification at sites of enthesitis.[11, 12, 13]

The initial presentation of AS generally occurs in the SI joints; involvement of the SI joints is required to establish the diagnosis. SI joint involvement is followed by involvement of the diskovertebral, apophyseal, costovertebral, and costotransverse joints and the paravertebral ligaments.

Early lesions include subchondral granulation tissue that erodes the joint and is replaced gradually by fibrocartilage and then ossification. This occurs in ligamentous and capsular attachment sites to bone and is called enthesitis.[14]

In the spine, this initial process occurs at the junction of the vertebrae and the anulus fibrosus of the intervertebral discs. The outer fibers of the discs eventually undergo ossification to form syndesmophytes. The condition progresses to the characteristic bamboo spine appearance.

Extra-articular involvement can include acute anterior uveitis and aortitis. Acute anterior uveitis occurs in 25-30% of patients and generally is unilateral. Symptoms include pain, lacrimation, photophobia, and blurred vision. Cardiac involvement including aortic insufficiency and conduction defects is generally a late finding and rare.[15]

Pulmonary involvement is secondary to inflammation of the costovertebral and costotransverse joints, which limits chest-wall range of motion (ROM). Pulmonary fibrosis is generally an asymptomatic incidental radiographic finding. Neurologic deficits are secondary to spinal fracture or cauda equina syndrome resulting from spinal stenosis. Spinal fracture is most common in the cervical spine.

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Etiology

The etiology of AS is unknown, but a combination of genetic and environmental factors works in concert to produce clinical disease.[16]

Genetic predisposition

The strong association of AS with HLA-B27 is direct evidence of the importance of genetic predisposition (see Table 1 below).[7, 8, 9, 17, 18, 19, 20] Of the various genotypic subtypes of HLA-B27, HLA-B*2705 has the strongest association with the spondyloarthropathies. HLA-B*2702, *2703, *2704, and *2707 are also associated with AS.[21] People who are homozygous for HLA-B27 are at a greater risk for AS than those who are heterozygous.[22] AS is more common in persons with a family history of AS or another seronegative spondyloarthropathy. The concordance rate in identical twins is 60% or less. HLA-B27 –restricted CD8+ (cytotoxic) T cells may play an important role in bacterial-related spondyloarthropathies such as reactive arthritis.[23]

Table 1. Association of Spondyloarthropathies With HLA-B27 (Open Table in a new window)

Population or Disease EntityHLA-B27 –Positive
Healthy whites8%
Healthy African Americans4%
Ankylosing spondylitis (whites)92%
Ankylosing spondylitis (African Americans)50%
Reactive arthritis60-80%
Psoriasis associated with spondylitis60%
IBD associated with spondylitis60%
Isolated acute anterior uveitis50%
Undifferentiated spondyloarthropathy20-25%

The shared amino acid sequence between the antigen-binding region of several HLA-B27 genotypic subtypes, especially HLA-B*2705, and nitrogenase from Klebsiella pneumoniae supports molecular mimicry as a possible mechanism for the induction of spondyloarthropathies in genetically susceptible hosts via an environmental stimulus, including bacteria in the GI tract.[24] The specifics of this relationship remain unclear.

Several other genes have been studied with respect to their potential involvement in the development of AS (see Table 2 below).

Table 2. Genetics of Ankylosing Spondylitis (Open Table in a new window)

GenesChromosome LocationGene Product/Function
Definitely associated



HLA-B27



IL-1 gene cluster



CYP 2D6



ARTS1 (ERAP1)



IL23R



6p21.3



2q12.1



22q13.2



5q15



1p31.1



Antigen presentation



Modulator of inflammation



Metabolism of xenobiotics



ER aminopeptidase 1



IL-23 receptor



Possibly associated



ANKH



HLA-DRB1



5p15



6p21.3



Ectopic mineralization



Antigen presentation



Not associated



TGF-ß, MMP3, IL-10, IL-6, Ig allotypes, TCR, TLR4, NOD2/CARD15, CD14, NFßBIL1, PTPN22, etc



MultipleMultiple

The interleukin (IL)-1 gene cluster is an important locus associated with susceptibility to AS.[25, 26] CYP 2D6 is weakly associated with AS.[18] ARTS1 is also associated with AS. This gene encodes the endoplasmic reticulum aminopeptidase, which cleaves cytokine receptors for IL-6, TNF-α, and IL-1 from the cell surface and is important in antigen presentation by class 1 major histocompatibility complex (MHC) molecules.[27, 19, 20]

IL23R, which encodes the receptor for IL-23, is also associated with AS.[27, 28, 29, 30, 19, 20] IL-23 promotes survival of TH17 CD4+ T cells. TH17 cells play an important role in inflammatory responses by producing various proinflammatory cytokines (eg, IL-17, IL-6, and TNF-α) and recruiting other inflammatory cells (eg, neutrophils) in inflammatory and infectious diseases. Thus, they may play an important role cells in the pathogenesis of AS and other spondyloarthropathies.[31]

Genes possibly associated with ankylosing spondylitis include ANKH and HLA-DRB1.[18]

Numerous genes have been excluded in the etiology of ankylosing spondylitis, including TGF-β, MMP3, IL-10, IL-6, immunoglobulin (Ig) allotypes, TCR, TLR4, NOD2/CARD15, CD14, NFbBIL1, and PTPN22, among others.[18]

Immunologic mechanisms

Another possible mechanism in the induction of AS is presentation of an arthritogenic peptide from enteric bacteria by specific HLA molecules. Many patients with AS have subclinical GI tract inflammation and elevated IgA antibodies directed against Klebsiella. The bacteria may invade the GI tract of a genetically susceptible host, leading to chronic inflammation and increased permeability. Over time, bacterial antigens containing arthritogenic peptides enter the organism via the bloodstream.

Localization of pathology to certain types of connective tissues (eg, entheses) may be explained by affinity of bacterial antigens to these specific sites. Biomechanical stress, such as that which occurs at entheses in the spine and feet, may predispose to clinical enthesitis at these sites.

The spondyloarthropathies are the only known autoimmune diseases linked to a HLA class-I rather than HLA class-II genes. The cytotoxic CD8+ T-cell response appears to be important; it would respond to antigen presented by HLA class-I molecules on the surface of cells. The association of spondyloarthropathies (eg, ReA) with HIV infection in certain areas of the world supports the relative importance of the CD8+ cytotoxic T-cell responses compared to the CD4+ helper cells in these conditions.

Environmental factors

AS does not develop in every person who is HLA-B27 –positive; thus, it is clear that environmental factors are important. Even first-degree relatives who are HLA-B27 –positive do not uniformly develop the disease. In fact, only 15-20% of such individuals develop the disease.

HLA-B27 –positive transgenic rats develop an illness similar to a spondyloarthropathy, with manifestations that include sacroiliitis, enthesitis, arthritis, skin and nail lesions, ocular inflammation, cardiac inflammation, and inflammation of the gastrointestinal and male genitourinary tracts.[32] The severity of the clinical disease correlates with the number of copies of HLA-B27 expressed in the transgenic animal.

HLA-B27 –positive transgenic rats that are raised in a germ-free environment do not develop clinical disease. Once introduced into a regular environment (ie, non–germ-free) and exposed to bacteria, the rats develop clinical manifestations of spondyloarthropathy.[33, 34]

Patients with AS may experience exacerbations after trauma. No scientific studies support trauma as a cause of AS.

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Epidemiology

AS is the most common of the classic spondyloarthropathies. Prevalence varies with the prevalence of the HLA-B27 gene in a given population, which increases with distance from the equator. In general, AS is more common in whites than in nonwhites. It occurs in 0.1-1% of the general population,[35, 36, 37] with the highest prevalence in northern European countries and the lowest in sub-Saharan Africa.[21, 38]

Approximately 1-2% of all people who are positive for HLA-B27 develop AS. This increases to 15-20% if they have a first-degree relative with HLA-B27 positive AS.[6, 16]

Prevalence data for USpA are scarce, although this disorder appears to be at least as common as AS, if not more so.[35] Its actual prevalence may be as high as 1-2% of the general population.

Age-related demographics

The age of onset of AS is usually from the late teens to age 40 years. Approximately 10%-20% of all patients experience symptom onset before age 16 years; in such patients, the disease is referred to as juvenile-onset AS. Onset of AS in persons older than 50 years is unusual, although diagnosis of mild or asymptomatic disease may be made at a later age.[39]

There is often a significant delay in diagnosis, usually occurring several years after the onset of inflammatory rheumatic symptoms. In a study of German and Austrian patients with AS, the age of onset of disease symptoms was 25 years in HLA-B27 –positive and 28 years in HLA-B27 –negative patients, with a delay in diagnosis of 8.5 years in HLA-B27 –positive and 11.4 years in HLA-B27 –negative patients.[40]

In a study of Turkish patients with AS, the age of onset of disease symptoms was 23 years, with a delay in diagnosis of 5.3 years in HLA-B27 –positive patients and 9.2 years in HLA-B27 –negative patients.[41] Patients with inflammatory back pain or a positive family history of AS had a shorter diagnostic delay.

USpA is generally found in young to middle-aged adults but can develop from late childhood into the fifth decade of life.[42]

Sex-related demographics

AS, in general, is diagnosed more frequently in males; the male-to-female ratio is 3:1.[6, 39] However, females may have milder or subclinical disease. The male-to-female ratio for USpA is 1:3.[42]

Race-related demographics

The prevalence of AS parallels the prevalence of HLA-B27 in the general population. The prevalence of HLA-B27 and AS is higher in whites and certain Native Americans than in African Americans, Asians, and other nonwhite ethnic groups.[21, 18] AS is least prevalent in sub-Saharan Africa. The less common juvenile-onset version of AS is more common among Native Americans, Mexicans, and persons in developing countries.

USpA is not associated as strongly with HLA-B27, although it is more prevalent in whites than in nonwhite ethnic groups.[42]

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Prognosis

The outcome in patients with spondyloarthropathies, including AS, is generally good compared with that in patients with a disease such as rheumatoid arthritis. Patients often require long-term anti-inflammatory therapy. Morbidity can occur from spinal and peripheral joint involvement or, rarely, extra-articular manifestations. Poor prognostic indicators include peripheral joint involvement, young age of onset, elevated erythrocyte sedimentation rate (ESR), and poor response to nonsteroidal anti-inflammatory drugs (NSAIDs).

At the onset of the disease, symptoms are generally unilateral and intermittent. As the disease progresses, pain and stiffness generally become more severe and more constant. Adequate exercise can improve symptoms and ROM.

Some patients have few, if any, symptoms. A significant portion of AS patients develop chronic progressive disease and develop disability due to spinal inflammation leading to fusion, often with thoracic kyphosis or erosive disease involving peripheral joints, especially the hips and shoulders. Patients with spinal fusion are prone to spinal fractures that may result in neurologic deficits. Most functional loss in AS occurs during the first 10 years of illness.[43]

Severe physical disability is not common among patients with AS. Problems with mobility occur in approximately 47% of patients. Disability is related to the duration of the disease, peripheral arthritis, cervical spine involvement, younger age at onset of symptoms, and coexisting illnesses. Disability has been demonstrated to improve with prolonged periods of exercise or surgical correction of peripheral joint and cervical spine involvement.

Most patients remain fully functional and continue working after the onset of symptoms.[44, 45, 46, 47, 48, 49] Vocational counseling has been demonstrated to decrease the risk of employment disability by more than 60%.[50] Although most patients are able to continue to work, as many as 37% change occupations to less physically demanding jobs as symptoms progress.

In rare cases, patients with severe long-standing AS develop significant extra-articular manifestations such as cardiovascular disease, including cardiac conduction defects and aortic regurgitation; pulmonary fibrosis; neurologic sequelae (eg, cauda equina syndrome); or amyloidosis. Patients with severe long-standing AS have a greater risk of mortality than the general population.[43] Death is more likely in the presence of either extra-articular manifestations or coexisting diseases.[51, 52]

Emotional problems related to the disease are reported in 20% of patients. Depression is more common among women, and contributing factors include the level of pain and functional disability involved.

USpA appears to carry a good-to-excellent prognosis, although some patients have chronic symptoms associated with functional disability. Erosive arthritis is very uncommon. Uveitis occasionally occurs and may be recurrent or chronic. Patients who develop sacroiliitis and spondylitis, by definition, have AS.[53, 42]

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Patient Education

Patient education is essential in disease management. Teach patients about the long-term nature of the illness and the use and toxicities of medications. Inform patients that proper exercise programs are useful in reducing symptoms and increasing ROM. Because of the joint involvement in the chest wall and the potential for pulmonary complications, include smoking cessation in recommendations. One 2011 study found that a history of smoking was associated with higher disease activity and decreased function in AS.[54]

Genetic counseling is useful in assisting patients with questions regarding the risk of family members developing AS or other seronegative spondyloarthropathies. Various patient support groups are available to assist in the education of these patients.

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Contributor Information and Disclosures
Author

Lawrence H Brent, MD  Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Coauthor(s)

Rajni Kalagate, MD  Resident Physician, Department of Internal Medicine, Albert Einstein Medical Center

Rajni Kalagate, MD is a member of the following medical societies: American Academy of Pediatrics and Indian Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

Jason C Eck, DO, MS Assistant Professor, Department of Orthopedics and Physical Rehabilitation, UMass Memorial Medical Center

Jason C Eck, DO, MS is a member of the following medical societies: American Osteopathic Academy of Orthopedics, American Osteopathic Association, International Society for the Study of the Lumbar Spine, and North American Spine Society

Disclosure: Medtronic Honoraria Speaking and teaching

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Scott D Hodges, DO Consulting Surgeon, Department of Orthopedic Surgery, Center for Sports Medicine and Orthopedics

Scott D Hodges, DO is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Medical Association, American Osteopathic Association, American Spinal Injury Association, North American Spine Society, Southern Medical Association, Southern Orthopaedic Association, and Tennessee Medical Association

Disclosure: Medtronic Royalty Consulting; Biomet Spine Royalty Consulting

S Craig Humphreys, MD Orthopedic Spine Surgeon, Department of Orthopedic Surgery, Center for Sports Medicine and Orthopedics

S Craig Humphreys, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Orthopaedic Surgeons, American Medical Association, American Spinal Injury Association, North American Spine Society, Southern Medical Association, Southern Orthopaedic Association, and Tennessee Medical Association

Disclosure: Nothing to disclose.

James F Kellam, MD Vice-Chair, Department of Orthopedic Surgery, Director of Orthopedic Trauma and Education, Carolinas Medical Center

James F Kellam, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Orthopaedic Trauma Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Center for the Advancement of Women's Health and Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

William O Shaffer, MD Professor, Vice-Chairman and Residency Program Director, Department of Orthopedic Surgery, University of Kentucky at Lexington

William O Shaffer, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, International Society for the Study of the Lumbar Spine, Kentucky Medical Association, Kentucky Orthopaedic Society, North American Spine Society, Southern Medical Association, and Southern Orthopaedic Association

Disclosure: DePuySpine 1997-2007 (not presently) Royalty Consulting; DePuySpine 2002-2007 (closed) Grant/research funds SacroPelvic Instrumentation Biomechanical Study; DePuyBiologics 2005-2008 (closed) Grant/research funds Healos study just closed; DePuySpine 2009 Consulting fee Design of Offset Modification of Expedium

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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  74. Naredo E, Batlle-Gualda E, García-Vivar ML, García-Aparicio AM, Fernández-Sueiro JL, Fernández-Prada M, et al. Power Doppler ultrasonography assessment of entheses in spondyloarthropathies: response to therapy of entheseal abnormalities. J Rheumatol. Oct 2010;37(10):2110-7. [Medline].

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  85. [Best Evidence] Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. Apr 2006;65(4):442-52. [Medline].

  86. Halm H, Metz-Stavenhagen P, Zielke K. Results of surgical correction of kyphotic deformities of the spine in ankylosing spondylitis on the basis of the modified arthritis impact measurement scales. Spine (Phila Pa 1976). Jul 15 1995;20(14):1612-9. [Medline].

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  88. Escalas C, Trijau S, Dougados M. Evaluation of the treatment effect of NSAIDs/TNF blockers according to different domains in ankylosing spondylitis: results of a meta-analysis. Rheumatology (Oxford). Jul 2010;49(7):1317-25. [Medline].

  89. Wanders A, Heijde D, Landewe R, et al. Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum. Jun 2005;52(6):1756-65. [Medline].

  90. Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis. Mar 2008;67(3):323-9. [Medline]. [Full Text].

  91. [Best Evidence] Chen J, Liu C. Is sulfasalazine effective in ankylosing spondylitis? A systematic review of randomized controlled trials. J Rheumatol. Apr 2006;33(4):722-31. [Medline].

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  94. Braun J, Pavelka K, Ramos-Remus C, Dimic A, Vlahos B, Freundlich B, et al. Clinical efficacy of etanercept versus sulfasalazine in ankylosing spondylitis subjects with peripheral joint involvement. J Rheumatol. Apr 2012;39(4):836-40. [Medline].

  95. Inman RD, Maksymowych WP. A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol. Jun 2010;37(6):1203-10. [Medline].

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  97. Braun J, Baraliakos X, Golder W, et al. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab: evaluation of a new scoring system. Arthritis Rheum. Apr 2003;48(4):1126-36. [Medline].

  98. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. May 2 2002;346(18):1349-56. [Medline].

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  100. [Best Evidence] van der Heijde D, Dijkmans B, Geusens P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. Feb 2005;52(2):582-91. [Medline].

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  103. van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. Jul 2006;54(7):2136-46. [Medline].

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  106. [Best Evidence] Chen J, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev. Oct 18 2006;CD004524. [Medline].

  107. [Best Evidence] van Denderen JC, van der Paardt M, Nurmohamed MT, de Ryck YM, Dijkmans BA, van der Horst-Bruinsma IE. Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis. Ann Rheum Dis. Dec 2005;64(12):1761-4. [Medline].

  108. van der Heijde D, Dougados M, Davis J, Weisman MH, Maksymowych W, Braun J, et al. ASsessment in Ankylosing Spondylitis International Working Group/Spondylitis Association of America recommendations for conducting clinical trials in ankylosing spondylitis. Arthritis Rheum. Feb 2005;52(2):386-94. [Medline].

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The family of spondyloarthropathies
This radiograph of the pelvis of a patient with ankylosing spondylitis shows bilateral sacroiliitis with sclerosis and narrowing of the sacroiliac joints.
This radiograph of the lumbar spine of a patient with ankylosing spondylitis shows sclerosis of vertebral margins, which are referred to as shining corners.
This radiograph of the lumbar spine of a patient with end-stage ankylosing spondylitis shows bridging syndesmophytes, resulting in bamboo spine.
This radiograph of the cervical spine of a patient with ankylosing spondylitis shows fusion of vertebral bodies due to bridging syndesmophytes.
This radiograph of the heel of a patient with undifferentiated spondyloarthropathy shows bony changes secondary to enthesitis, with an erosion at the insertion of the Achilles tendon and periosteal new-bone formation at the insertion of the plantar fascia on the calcaneus.
This 15-year-old female patient presented with recent onset of right-sided low back pain. Plain radiography findings were normal.
MRI of the same patient whose radiography findings were normal (Picture 7). She underwent further evaluation, including MRI. The MRI (short tau inversion recovery [STIR]) showed increased sinal intensity in the right sacroiliac joint, revealing sacroiliitis. Other laboratory study findings were essentially normal. The patient was started on indomethacin and rapidly improved.
Patient with ankylosing spondylitis affecting cervical and upper thoracic spine. Patient's spine has been fused in flexed position.
Posterior view of patient with ankylosing spondylitis affecting cervical and upper thoracic spine. Patient's spine has been fused in flexed position.
Anteroposterior radiograph of sacroiliac joint of patient with ankylosing spondylitis. Bilateral sacroiliitis with sclerosis can be observed.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus can be observed at multiple levels, which has led to fusion of spine with abnormal curvature.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis. Ossification of anulus fibrosus at multiple levels and squaring of vertebral bodies can be observed.
Anteroposterior radiograph of spine of patient with ankylosing spondylitis.
Anteroposterior (left) and lateral (right) radiographs of patient with ankylosing spondylitis.
Radiographs of hand (top) and arm (bottom) of patient with peripheral involvement of ankylosing spondylitis. Fusion of joint spaces and deformity can be observed.
Sagittal MRI of thoracolumbar spine of a patient with ankylosing spondylitis. Degenerative disc disease and bridging osteophytes can be observed at multiple levels.
Radiograph shows vertebral fracture in patient with ankylosing spondylitis.
Table 1. Association of Spondyloarthropathies With HLA-B27
Population or Disease EntityHLA-B27 –Positive
Healthy whites8%
Healthy African Americans4%
Ankylosing spondylitis (whites)92%
Ankylosing spondylitis (African Americans)50%
Reactive arthritis60-80%
Psoriasis associated with spondylitis60%
IBD associated with spondylitis60%
Isolated acute anterior uveitis50%
Undifferentiated spondyloarthropathy20-25%
Table 2. Genetics of Ankylosing Spondylitis
GenesChromosome LocationGene Product/Function
Definitely associated



HLA-B27



IL-1 gene cluster



CYP 2D6



ARTS1 (ERAP1)



IL23R



6p21.3



2q12.1



22q13.2



5q15



1p31.1



Antigen presentation



Modulator of inflammation



Metabolism of xenobiotics



ER aminopeptidase 1



IL-23 receptor



Possibly associated



ANKH



HLA-DRB1



5p15



6p21.3



Ectopic mineralization



Antigen presentation



Not associated



TGF-ß, MMP3, IL-10, IL-6, Ig allotypes, TCR, TLR4, NOD2/CARD15, CD14, NFßBIL1, PTPN22, etc



MultipleMultiple
Table 3. Diagnostic Criteria for Undifferentiated Spondyloarthropathy Using Modified Amor Criteria
Inclusion CriteriaExclusion Criteria
Inflammatory back pain1 pointDiagnosis of specific spondyloarthropathy
Unilateral buttock pain1 pointSacroiliitis on radiograph = grade 2
Alternating buttock pain2 pointsPrecipitating genitourinary/gastrointestinal infection
Enthesitis2 pointsPsoriasis
Peripheral arthritis2 pointsKeratoderma blennorrhagicum
Dactylitis (sausage digit)2 pointsInflammatory bowel disease (Crohn disease or ulcerative colitis)
Acute anterior uveitis2 pointsPositive rheumatoid factor
HLA-B27 –positive or family history of spondyloarthropathy2 pointsPositive antinuclear antibody, titer > 1:80
Good response to nonsteroidal anti-inflammatory drugs2 points
Diagnosis of spondyloarthropathy with 6 or more points
Table 4. Clinical and Laboratory Features of Undifferentiated Spondyloarthropathy
Clinical or Laboratory FeatureFrequency
Inflammatory back pain90%
Buttock pain80%
Enthesitis75%
Peripheral arthritis40%
Dactylitis (sausage digits)20%
Acute anterior uveitis1-2%
Fatigue55%
Elevated ESR32%
HLA-B27 –positive25%
ESR = erythrocyte sedimentation rate.
Table 5. ESSG and Amor Criteria for Diagnosis of Spondyloarthropathy
ESSG CriteriaAmor Criteria*
Inflammatory spinal pain or synovitis and one of the following:Inflammatory back pain1 point
Alternating buttock painUnilateral buttock pain1 point
EnthesitisAlternating buttock pain2 points
SacroiliitisEnthesitis2 points
IBDPeripheral arthritis2 points
Positive family history of spondyloarthropathyDactylitis (sausage digit)2 points
Acute anterior uveitis2 points
HLA-B27 –positive or family history of spondyloarthropathy2 points
Good response to NSAIDs2 points
*Diagnosis of spondyloarthropathy with 6 or more points.



European Spondyloarthropathy Study Group (ESSG); IBD = inflammatory bowel disease; NSAID = nonsteroidal anti-inflammatory drug.



Table 6. New York and Rome Criteria for Diagnosis of Ankylosing Spondylitis
New York CriteriaRome Criteria
  • Low back pain with inflammatory characteristics
  • Limitation of lumbar spine motion in sagittal and frontal planes
  • Decreased chest expansion
  • Bilateral sacroiliitis grade 2 or higher
  • Unilateral sacroiliitis grade 3 or higher
  • Low back pain and stiffness for >3 months that is not relieved by rest
  • Pain and stiffness in the thoracic region
  • Limited motion in the lumbar spine
  • Limited chest expansion
  • History of uveitis
Definite ankylosing spondylitis when the fourth or fifth criterion mentioned presents with any clinical criteriaDiagnosis of ankylosing spondylitis when any clinical criteria present with bilateral sacroiliitis grade 2 or higher
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