Ankylosing Spondylitis


Article Author:
Kyle Wenker


Article Editor:
Jessilin Quint


Editors In Chief:
Sisira Reddy
Joseph Nahas
Chokkalingam Siva


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
11/14/2018 3:44:25 PM

Introduction

Ankylosing spondylitis (AS) is a chronic, inflammatory disease of the axial spine that can manifest with various clinical signs and symptoms. Chronic back pain and progressive spinal stiffness are the most common features of the disease. Involvement of the spine and sacroiliac (SI) joints, peripheral joints, digits, entheses are characteristic of the disease. Impaired spinal mobility, postural abnormalities, buttock pain, hip pain, peripheral arthritis, enthesitis, and dactylitis ("sausage digits") are all associated with AS.

Extraskeletal organs may also be affected by this disease. The most common extraarticular manifestations of AS include inflammatory bowel disease (up to 50%), acute anterior uveitis (25% to 35%), and psoriasis (approximately 10%). AS is also associated with an increased risk of cardiovascular disease. The cause of this increased risk has been postulated to be due to the systemic inflammation evident in AS. Pulmonary complications are also associated with AS, as diminished chest wall expansion and decreased spinal mobility predispose patients to a restrictive pulmonary pattern.

Finally, AS predisposes people to at least a two-fold increased incidence of vertebral fragility fractures. These patients are also at increased risk of atlantoaxial subluxation, spinal cord injury, and, rarely, cauda equina syndrome.[1][2][3]

Etiology

The cause of AS remains largely idiopathic, but there seems to be a correlation between the prevalence of AS in a given population and the prevalence of human leukocyte antigen (HLA)-B27 in that same population. Among people who are HLA-B27 positive, the prevalence of AS is approximately 5% to 6%. In the United States, the prevalence of HLA-B27 varies among ethnic groups. According to a 2009 survey, prevalence rates of HLA-B27 were 7.5% among non-Hispanic whites, 4.6% among Mexican-Americans, and 1.1% among non-Hispanic blacks.[4][5]

Epidemiology

AS is typically diagnosed in people younger than 40 years, and about 80% of patients develop first symptoms when they are younger than 30 years. Less than 5% of patients present when they are older than 45 years. AS is more common among men than among women. There is an increased risk in relatives of affected patients.[6]

Pathophysiology

AS is a chronic inflammatory disease with an insidious onset. Progressive musculoskeletal, and often extraskeletal, signs and symptoms are characteristic of the disease. The rate of progression can vary from one patient to the next.

History and Physical

A comprehensive, full-body evaluation should be performed in patients suspected of having AS due to the pervasive nature of the disease and susceptibility to multi-organ system involvement. Almost all patients will complain of back pain to some degree. The characteristic type of back pain in AS is "inflammatory" in nature. Inflammatory back pain typically exhibits at least four of the five following characteristics: age of onset less than 40 years, insidious onset, improvement with exercise, no improvement with rest, and pain at night with an improvement upon arising. Spinal stiffness, immobility, and postural changes, especially hyperkyphosis, are also commonly seen. History and physical exam should address all systems, as AS can have several axial and peripheral musculoskeletal manifestations, as well as extra-articular features. A detailed medical history should be obtained to rule in/out any correlated conditions (e.g., psoriasis, IBD, uveitis, among others).

Evaluation

Laboratory findings in AS are generally nonspecific but may help assist with diagnosis. About 50% to 70% of patients with active AS have elevated acute phase reactants, such as erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP). A normal ESR and CRP, however, should not exclude the disease.[7][8][9]

A number of imaging abnormalities, especially those affecting the spine and sacroiliac joints, are characteristic of AS. In fact, according to the Assessment of Spondyloarthritis International Society (ASAS) 2009 axial SpA criteria, evidence of sacroiliitis on imaging (radiographic or MRI) is a major inclusion criteria for AS. A standardized plain radiographic grading scale exists for sacroiliitis, which ranges from normal (0) to most severe (IV), as detailed below.

  • 0: Normal SI joint width, sharp joint margins
  • I: Suspicious
  • II: Sclerosis, some erosions
  • III: Severe erosions, pseudo dilation of the joint space, partial ankylosis
  • IV: Complete ankylosis

In the first few years of AS, plain radiographic changes in the SI joints can be very subtle, but within the first decade will usually become more obvious. Subchondral erosions, sclerosis, and joint fusion are the most obvious abnormalities, and these radiographic changes are typically symmetric.

A series of plain radiographic changes characteristic of AS can progressively develop over the course of the disease. An early sign is "squaring" of the vertebral bodies, best seen on lateral x-ray. This is seen as a loss of normal concavity of the anterior and posterior borders of the vertebral body due to inflammation and bone deposition. Romanus lesions, or the "shiny corner sign," can also be seen on this radiographic view in early stages. These lesions are characterized by small erosions and reactive sclerosis at the corners of the vertebral bodies. Late-stage findings include ankylosis (fusion) of the facet joints of the spine, syndesmophytes, and calcification of the anterior longitudinal ligament, supraspinous ligaments, and interspinous ligaments. This calcification may be seen on imaging as the "dagger sign," which is represented as a single radiodense line running vertically down the spine on frontal radiographs. The classic radiographic finding in late-stage AS is the "bamboo spine sign," which refers to the vertebral body fusion by syndesmophytes. A bamboo spine typically involves the thoracolumbar and/or lumbosacral junctions. It is this fusion of the spine that predisposes the patient to progressive back stiffness.

While plain radiography is the first-line imaging modality in AS, MRI may be needed to reveal more subtle abnormalities such as fatty changes and/or inflammatory changes. Active SI joint inflammatory lesions appear as bone marrow edema (BME) on short tau inversion recovery (STIR) and T2-weighted images with fat suppression. It should be noted that the presence of BME on MRI can also be seen in up to 23% of patients with mechanical back pain and 7% of healthy people.[10]

Treatment / Management

Treatment goals should focus on relieving pain and stiffness, maintaining axial spine motion and functional ability, and preventing spinal complications. Non-pharmacologic interventions should include regular exercise, postural training, and physical therapy. First-line medication therapy is with long-term, daily non-steroidal anti-inflammatory drugs (NSAIDs). Should NSAIDs not provide adequate relief, they can be combined with or substituted for tumor necrosis factor inhibitors (TNF-Is) such as adalimumab, infliximab, or etanercept. Response to NSAIDs should be assessed 4 to 6 weeks after initiation and 12 weeks following initiation of TNF-Is. Systemic glucocorticoids are not recommended, but local steroid injections may be considered. Specialist referrals may be warranted based on the patient's clinical picture, potential complications, and/or extra-articular manifestations of the disease. Rheumatologists may assist in a formal diagnosis, management, and monitoring, while dermatologists, ophthalmologists, and gastroenterologists may assist with associated non-musculoskeletal features of AS.[11][1][12]

Differential Diagnosis

Certain diseases and conditions can mimic AS and must be ruled out. These include, but are not limited to, mechanical low back pain, lumbar spinal stenosis, rheumatoid arthritis, and diffuse idiopathic skeletal hyperostosis (DISH). Each of these diagnoses has similarities with AS, but their differences should be ruled in or out for accurate diagnosis. 

Mechanical back pain can be differentiated from AS by the onset of symptoms, as mechanical back pain can present at any age, while AS typically presents before age 40. Unlike AS, pain improves with rest, and morning stiffness is mild and short-lived. Mechanical back pain is also not associated with peripheral arthritis or extraskeletal manifestations, as AS is.

Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal that exerts pressure on the spinal cord. Like AS, it may present with chronic back pain and morning stiffness. Unlike AS, however, LSS usually presents in patients older than 60 years, is not associated with peripheral arthritis or extraskeletal features, and response to NSAIDs is variable.

Rheumatoid arthritis (RA) is another chronic inflammatory disorder of the joints that often presents with progressive back pain and morning stiffness in patients 40 or younger, similar to AS. However, peripheral arthritis is extremely common in RA, unlike in AS. In addition, rheumatoid nodules are pathognomonic for RA but are not usually present with AS.

Diffuse idiopathic skeletal hyperostosis (DISH) is a degenerative disorder characterized by ossification in the spine occurring primarily in the anterior longitudinal ligament, paravertebral tissues, and peripheral aspect of the annulus fibrosus. Similar to AS, the DISH may present with a history of postural changes and back pain. Unlike AS, which is an inflammatory disorder, the DISH does not have inflammatory characteristics such as morning stiffness or improvement with exercise but not with rest. DISH also shows no evidence of sacroiliitis on radiographs.

Prognosis

While the younger age of onset in AS patients is associated with poorer function outcomes, severe physical disability is uncommon. Most patients remain fully functional and able to work. Patients with severe, long-standing disease have greater mortality compared with the general population, predominantly due to cardiovascular complications.

Complications

  • Chronic pain
  • Disability
  • Aortic regurgitation
  • Pulmonary fibrosis
  • Cauda Equina syndrome
  • Mood disorders

Postoperative and Rehabilitation Care

To remain functional, physical therapy is highly recommended. Both water therapy and swimming are known to help maintain fitness and lower the morbidity.

Pearls and Other Issues

Pitfalls: The possibility of vertebral fracture should always be considered in patients with AS, even after minor trauma. Patients with AS are at increased risk of vertebral fracture and subluxation, especially of the cervical spine. Therefore, these patients are more susceptible to neurologic compromise.

Prevention of disease morbidity can be achieved with exercise, physical therapy, tailored pharmacologic intervention, and regimented follow-up appointments with physicians.

Enhancing Healthcare Team Outcomes

Ankylosing spondylitis is a systemic disorder that can affect many organ systems and hence an interprofessional team approach is recommended to avoid the morbidity. 

  • Rheumatologist to evaluate and manage the acute symptoms and address any coexisting spondyloarthropathies.
  • Gastroenterologist to assess for inflammatory bowel disease
  • Ophthalmologist to assess for anterior uveitis
  • Cardiologist to assess for heart block or valvular involvement
  • Physical therapy to help with function
  • Neurologist to assess for nerve compression syndromes
  • Pharmacist to monitor for drug interactions and dependence on analgesics
  • Nurse to educate the patient on the management of daily living activities

There are many reports indicating that an interprofessional approach to ankylosing spondylitis can improve function, lower pain and increase the quality of life. [13][14] (Level II)

Evidence-based Medicine

Meta-analysis of many studies has revealed that those who participate in an exercise program have a much better outcome than those who lead a sedentary lifestyle. (Level II) Unfortunately, those patients with large symptom burden at the time of diagnosis usually have poor response rates and are often lost to follow up. One way to retain these patients is by starting an education program early in the disease.  [15][16][17](Level V)

 

 

 


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Ankylosing Spondylitis - Questions

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Which is not true of ankylosing spondylitis?



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Bamboo spine is commonly seen in what condition?



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A 17-year-old male complains of low back pain with morning stiffness. The pain is decreased with stretching. The patient has no gastrointestinal, genitourinary, or neurologic symptoms. The patient is unable to touch his toes, but his range of motion at other joints is normal. There is tenderness over the lumbosacral spine and pain over the sacroiliac joints. Which of the following is the most likely diagnosis?



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A young male presents with back pain that started several months ago and has steadily gotten worse. He also notes that he feels stiff in his joints but this gets better during the day. Lately, he has been having pain in the buttocks with no radiation. He denies any trauma, travel, or use of any medications. He did have an MRI which revealed erosions with sacroiliitis bilaterally. Which of the following treatments is not appropriate for him?



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A patient diagnosed with ankylosing spondylitis is treated with naproxen 500 mg twice a day and physical therapy. He is not showing improvement. Which of the following would be appropriate for this patient?



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A patient with ankylosing spondylitis has declined prescription therapy and he has been taking over-the-counter naproxen. He complains of neck stiffness, a decreased range of motion, "crampy" abdominal pain, loose stools with hematochezia, and dyspnea upon mild exertion. Which of the following would not be an appropriate component of this patient's management?



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A 25-year-old male presents complaining of back pain that has been present for 2 months. He denies any trauma but says that he has a family history of joint problems. He says the pain is worse in the morning. On physical exam, he is tender to palpation over the lumbar spine and has limited chest expansion. He also is unable to touch his toes with his fingers while standing. Bloodwork reveals an elevated erythrocyte sedimentation rate and mild anemia. X-rays reveal that there is "squaring" of the lumbar vertebrae and symmetrical syndesmophyte formation ("bamboo spine"). Which of the following is not true regarding this condition?



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Which of the following disorders is associated with HLA B27?



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Which of the following disorders most often affects males?



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In which of the following will a bamboo spine be most likely?



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A young male complains of back pain that is improved with exercise. He has no history of gastrointestinal illness or symptoms of urethritis. On exam, he is found to have restricted lumbar mobility, tenderness of sacroiliac joints, and an x-ray showing sacroiliac sclerosis. Which of the following is true?



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A male presents with a long history of low back and sacral pain. He denies any injury. He did have a distant bout of severe diarrhea. Exam reveals marked tenderness in the axial and peripheral joints. He also appears to have marked swelling of the tendons on his feet. On x-ray, he has subchondral sclerosis and erosions of the sacroiliac joints, and vertebral squaring. Which extra-articular manifestation is often seen in these patients?



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What type of heart disorder is often present in patients with ankylosing spondylitis?



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A male presents with a long history of low back and sacral pain. He denies any injury except for a distant bout of severe diarrhea. Exam reveals marked tenderness in the axial and peripheral joints. He also appears to have marked swelling of the tendons on his feet. On x-ray, he has subchondral sclerosis and erosions of the sacroiliac joints, and vertebral squaring. He was started on an NSAID. How often should x-ray studies be obtained to monitor his progress?



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Which of the following peripheral joints are commonly involved in ankylosing spondylitis?



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Where is the most common location of peripheral enthesitis in patients with ankylosing spondylitis?



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What is the most common extraarticular manifestation of ankylosing spondylitis?



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Patients with ankylosing spondylitis often have elevated IgA antibodies directed towards which of the following?



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The diagnosis of ankylosing spondylitis is made by which of the following?



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Bamboo spine is commonly seen in patients with which of the following?



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Which of the following is used to treat ankylosing spondylitis?



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A male presents with 12 weeks of low back and sacral pain worse in morning. He denies any injury or any recent illness. Exam reveals marked tenderness in the axial and peripheral joints. He also appears to have marked swelling of the tendons on his feet. On x-ray, he has subchondral sclerosis and erosions of the sacroiliac joints, and vertebral squaring. What is the average age of onset of this disorder?



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Which of the following is useful for making a definitive diagnosis of ankylosing spondylitis (AS)?



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A 38-year-old male presents with low back pain. X-rays of the hip joints reveal inflammatory lesions of the hip and pelvic joints. Which of the following would you NOT expect to see in the patient?



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An 17-year-old male presents complaining of back pain that is improved with exercise with no history of gastrointestinal illness or symptoms of urethritis and is found on exam to have restricted lumbar mobility, tenderness of sacroiliac joints, and an x-ray showing sacroiliac sclerosis. Which of the following in this case is TRUE?



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A 19-year-old male presents complaining of back pain that is improved with exercise. He has no history of gastrointestinal illness or symptoms of urethritis. On exam, he has restricted lumbar mobility, tenderness of the sacroiliac joints, and an x-ray showing sacroiliac sclerosis. Which of the following statements regarding this patient is most likely?



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What joint is most commonly involved in ankylosing spondylitis?



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What is the best treatment for a 27 year old with ankylosing spondylitis?



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Which of the following is used in long term treatment of ankylosing spondylosis?



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Which of the following is most commonly seen in patients with ankylosing spondylitis?



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A 17-year-old male reports a 9-month history of low back pain, worse in the morning and after periods of immobility. The pain awakens the patient at night. The exam is remarkable for decreased mobility of the lumbar spine, pain over the ischial tuberosities, greater trochanters, and iliac crests. An x-ray of the pelvis shows sclerosis and erosions of bilateral sacroiliac joints. Select the test that is most probably positive.



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A 27-year-old male has had low back pain and stiffness for two years. The plain radiographs show bilateral sacroiliitis. What is the most likely gene association?



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Which of the following is most useful for making a definitive diagnosis of ankylosing spondylitis (AS)?



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Which of the following is the most common spondyloarthropathy?



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A male patient presents with a 3-year history of low back pain and stiffness. Lumbar x-ray shows bilateral sacroiliitis. Which HLA type is most likely present?



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A male presents with a long history of low back and sacral pain. He denies any injury and admits to a distant bout of severe diarrhea. An exam reveals marked tenderness in the axial and peripheral joints. He also appears to have marked swelling of the tendons in his feet. On x-ray, he has subchondral sclerosis and erosions of the sacroiliac joints and vertebral squaring. He was started on an NSAID but has not improved. At this point, what is the best treatment?



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Select the true statement about the treatment of ankylosing spondylitis (AS).



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A 28-year old male presents with 12 weeks of low back and sacral pain worse in the morning. He denies any injury or any recent illness. Exam reveals marked tenderness in the axial and peripheral joints. He also appears to have marked swelling of the tendons on his feet. On x-ray, he has subchondral sclerosis and erosions of the sacroiliac joints. What other feature on plain x-ray may be typical of his disease?



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A 17-year-old male has low back pain and stiffness. He has reduced flexion of the spine, chest expansion of fewer than 2.5 centimeters, and sacroiliac tenderness. What is the most likely diagnosis?



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Which of the following diseases predominantly causes stiffening and inflammation of the spinal joints?



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A 38-year-old male is following up with his provider regarding low back pain. A physical exam shows painful and diminished forward flexion with tenderness over both buttocks. Laboratory studies show an elevated erythrocyte sedimentation rate. Rheumatoid factor and antinuclear antibody are negative. HLA-B27 is positive. X-rays of his lumbar spine and sacroiliac joints are normal. He is diagnosed with ankylosing spondylitis. Which of the following is the appropriate first-line pharmacotherapy?



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A 28-year-old Burmese male with a history of recently diagnosed ankylosing spondylitis comes to your office. He emigrated from Burma 6 years ago. He has tried ibuprofen and meloxicam at high doses to control his lower back symptoms with very limited relief. His symptoms are greatly affecting his work performance, and he is interested in further controlling them. He denies any other symptoms such as fever, fatigue, cough, and sputum production. You discuss with him beginning TNF-inhibitors to which he is agreeable. The chest radiograph is normal and interferon gamma release assay is positive. The rest of his electrolytes, kidney function, and liver function are all normal. What is the next step in care?



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Which of the following conditions is not associated with ankylosing spondylitis?



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According to the 2011 Assessment of Spondyloarthritis International Society (ASAS) peripheral spondyloarthropathy (SpA) criteria, which of the following is not considered to be a major inclusion criterion for diagnosing ankylosing spondylitis (AS)?



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A 35-year-old man complains of chronic back pain that had gradual onset lasts several hours a day, and is worse with rest. He can not sleep because the pain gets worse overnight. He is a construction worker with normal vital signs and point tenderness over bilateral hip areas. What is the most likely diagnosis?



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A 35-year-old woman with a history of celiac's disease presents to her primary provider complaining of worsening low back pain for the past one year. She notes pain is worse in the morning and additionally notes bilateral hip pain. On examination, her vital signs are within normal limits. She has a positive Schober's test and pain with flexion, abduction and external rotation of her hips bilaterally. An x-ray of the pelvis is pending; what will it most likely show?



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Ankylosing Spondylitis - References

References

Proft F,Poddubnyy D, Ankylosing spondylitis and axial spondyloarthritis: recent insights and impact of new classification criteria. Therapeutic advances in musculoskeletal disease. 2018 Jun     [PubMed]
Bridgewood C,Watad A,Cuthbert RJ,McGonagle D, Spondyloarthritis: new insights into clinical aspects, translational immunology and therapeutics. Current opinion in rheumatology. 2018 Sep     [PubMed]
Watad A,Cuthbert RJ,Amital H,McGonagle D, Enthesitis: Much More Than Focal Insertion Point Inflammation. Current rheumatology reports. 2018 May 30     [PubMed]
Mahmoudi M,Garshasbi M,Ashraf-Ganjouei A,Javinani A,Vojdanian M,Saafi M,Ahmadzadeh N,Jamshidi A, Association between rs6759298 and Ankylosing Spondylitis in Iranian Population. Avicenna journal of medical biotechnology. 2018 Jul-Sep     [PubMed]
van den Berg R,Jongbloed EM,de Schepper EIT,Bierma-Zeinstra SMA,Koes BW,Luijsterburg PAJ, The association between pro-inflammatory biomarkers and nonspecific low back pain: a systematic review. The spine journal : official journal of the North American Spine Society. 2018 Jun 27     [PubMed]
Wang R,Ward MM, Epidemiology of axial spondyloarthritis: an update. Current opinion in rheumatology. 2018 Mar     [PubMed]
Aloush V,Dotan I,Ablin JN,Elkayam O, Evaluating IBD-specific antiglycan antibodies in serum of patients with spondyloarthritis and rheumatoid arthritis: are they really specific? Clinical and experimental rheumatology. 2018 Jun 25     [PubMed]
Rabelo CF,Baptista TSA,Petersen LE,Bauer ME,Keiserman MW,Staub HL, Serum IL-6 correlates with axial mobility index (Bath Ankylosing Spondylitis Metrology Index) in Brazilian patients with ankylosing spondylitis. Open access rheumatology : research and reviews. 2018     [PubMed]
Rahbar MH,Lee M,Hessabi M,Tahanan A,Brown MA,Learch TJ,Diekman LA,Weisman MH,Reveille JD, Harmonization, data management, and statistical issues related to prospective multicenter studies in Ankylosing spondylitis (AS): Experience from the Prospective Study Of Ankylosing Spondylitis (PSOAS) cohort. Contemporary clinical trials communications. 2018 Sep     [PubMed]
Kucybała I,Urbanik A,Wojciechowski W, Radiologic approach to axial spondyloarthritis: where are we now and where are we heading? Rheumatology international. 2018 Aug 21     [PubMed]
Kivitz AJ,Wagner U,Dokoupilova E,Supronik J,Martin R,Talloczy Z,Richards HB,Porter B, Efficacy and Safety of Secukinumab 150 mg with and Without Loading Regimen in Ankylosing Spondylitis: 104-week Results from MEASURE 4 Study. Rheumatology and therapy. 2018 Aug 18     [PubMed]
Liang H,Tian X,Liu XL,Wang SY,Dai Y,Kang L,Chen LS,Jin LF, The comparative efficacy of group- versus home-based exercise programs in patients with ankylosing spondylitis: Protocol for a meta-analysis. Medicine. 2018 Jul     [PubMed]
Armuzzi A,Felice C,Lubrano E,Cantini F,Castiglione F,Gionchetti P,Orlando A,Salvarani C,Scarpa R,Marchesoni A,Vecchi M,Olivieri I, Multidisciplinary management of patients with coexisting inflammatory bowel disease and spondyloarthritis: A Delphi consensus among Italian experts. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2017 Dec     [PubMed]
Agca R,Heslinga SC,Rollefstad S,Heslinga M,McInnes IB,Peters MJ,Kvien TK,Dougados M,Radner H,Atzeni F,Primdahl J,Södergren A,Wallberg Jonsson S,van Rompay J,Zabalan C,Pedersen TR,Jacobsson L,de Vlam K,Gonzalez-Gay MA,Semb AG,Kitas GD,Smulders YM,Szekanecz Z,Sattar N,Symmons DP,Nurmohamed MT, EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the rheumatic diseases. 2017 Jan     [PubMed]
Krabbe S,Glintborg B,Østergaard M,Hetland ML, Extremely poor patient-reported outcomes are associated with lack of clinical response and decreased retention rate of tumour necrosis factor inhibitor treatment in patients with axial spondyloarthritis. Scandinavian journal of rheumatology. 2018 Aug 13     [PubMed]
Deminger A,Klingberg E,Geijer M,Göthlin J,Hedberg M,Rehnberg E,Carlsten H,Jacobsson LT,Forsblad-d'Elia H, A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis. Arthritis research     [PubMed]
Torre-Alonso JC,Queiro R,Comellas M,Lizán L,Blanch C, Patient-reported outcomes in European spondyloarthritis patients: a systematic review of the literature. Patient preference and adherence. 2018     [PubMed]

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