MRD 570 – EVIDENCE-BASED PRACTICE IN MEDICAL IMAGING

ANKYLOSING SPONDYLITIS

Noor Farahuda Binti Mustafah MaarofLecturer’s Name: Haji Mohamed Nadzry Bin Mohd

Yusoff

1.0 – Brief Description of Ankylosing Spondilitis

2.0 – Etiology & Pathophysiology 3.0 – Clinical manifestation 4.0 – Imaging Modalities Utilized in Diagnosing

Ankylosing Spondylitis 5.0 – Roles of the Imaging Modalities in

Diagnosing Ankylosing Spondylitis 6.0 – Image Features of Ankylosing Spondylitis

in the Imaging Modalities 7.0 – References

LIST OF CONTENT

1.0 - ANKYLOSING SPONDYLITIS

WHAT IT IS ABOUT?

Ankylos: joints’ stiffening; spondylitis: vertebra inflammation, while Ankylosing Spondylitis refers to the inflammation of the vertebrae that may result in stiffness. It is a type of inflammatory arthritis and autoimmune disease.

According to Ehrenfeld (2012), Ankylosing Spondylitis is the common form of spondyloarthropathies (SpA), or also known as spondyloarthritides (SpAs), a group of various related inflammatory arthritis.

“Inflammation of the axial skeleton, large peripheral joints, and digits, characterized by nocturnal back pain, back stiffness, accentuated kyphosis, constitutional symptoms, aortitis, cardiac conduction abnormalities, and anterior uveitis” (Porter & Kaplan, 2013)

2.0 – ETIOLOGY & PATHOPHYSIOLO

GY

Ankylosing Spondylitis is believed due to genetic predisposition. Human Leukocyte Antigen (HLA)-B27 is the main gene associated with susceptibility to Akylosing Spondylitis (Porter & Kaplan, 2013)

Molecular mimicry hypothesis suggest that there are possibly cross reactive between the Klebsiella Microbe and HLA-B27 that lead to the formation of Ankylosing Spondylitis (Ebringer, 2013)

Ankylosing Spondylitis affects men three times more often than women, developing most commonly between ages of 20 and 40 (Kowalczyk & Mace, 2009)About 20 times more often among the first degree relatives of the patient than other person tends to have this disease (Porter & Kaplan, 2013)

A man whose is a positive HLA-B27 allele more likely to suffer from Ankylosing Spondylitis with the presence of Klebsiella microbes, an infection in the gut.

ETIOLOGY OF ANKYLOSING SPONDYLITIS

Infection in the gut by Klebsiella

microbes

Pathogenic agents (anti-QTDRED and

anti-DRDE Klebsiella

antibodies) is produced.

The binding of anti-QTDRED with HLA-B27 will induced

the tissue damage, which in turn will produce localized

inflammation

The inflammatory cells that erode the

bone and fibrocartilage will then infiltrate the

fibrous tissue of the joint capsule.

Repair of the cartilaginous

structures begins with the

proliferation of fibroblasts, which

synthesize and secrete collagen.

The fibrous scar tissue that resulted from the collagen

formation will undergoes

calcification, causing the joints

to fuse or lose flexibility.

PATHOPHYSIOLOGY

OF ANKYLOSING SPONDYLITIS

(Ebringer, 2013)

3.0 - CLINICAL MANIFESTATIO

N(SIGNS &

SYMPTOMS)

The Most Common Signs and Symptoms of Ankylosing

SpondylitisWeight lossKyphosisIritis/ UveitisEnthesitisEnthesophyte

Pain and stiffness that worse in immobility, especially during early morning and late night

More common at the area of axial skeleton (spine, sacroiliac joints, neck)Some feel pain at the peripheral joint area (knee, heel, shoulder)

Mild feverLoss of appetiteShort of breathFatigue and general discomfort Movement difficulty / Ankylosis

Sign: an objective manifestation that can be detected by physician during examination

Symptom: patient’s perception of the disease

Spondylitis Association of America, 2013

4.0 – IMAGING MODALITIES

UTILIZEDin Diagnosing Ankylosing

Spondylitis

MODALITIES USED IN

EVALUATING ANKYLOSIN

G SPONDYLITI

S

1) Conventional Radiography

3) Computed Tomography

2) Magnetic Resonance Imaging

4) Nuclear Medicine Imaging

5) Ultrasonography

5.0 - ROLE OF IMAGING

MODALITIESin Diagnosing Ankylosing

Spondylitis

Is the cornerstone for diagnosis of Ankylosing Spondylitis after the evaluation of clinical and laboratory finding. However, the visualization of Sacroiliitis and Bamboo Spine indicate that the disease is in advanced.

Has high spatial resolution and offer high contrast for certain structures, which are bone (calcium), soft tissue and fat.

Better visualization of bony skeletal and detect any bony/ joint space changes due to inflammation as it has inherent contrast (high bone-tissue contrast)

However, the inherent contrast of soft tissues and surrounding organs (low contrast, thus make the structures appear with same density) make the detection of any soft tissue abnormalities become difficult.

Unable to identify for an active inflammation as it was only 54.4% sensitive, but 97.8% specific for detection of structural changes due to Ankylosing Spondylitis

(Ostergaard & Lambert, 2012)

Well-known these days as a selection tool for early diagnosis of Ankylosing Spondylitis.

Was 95% sensitive and 100% specific in diagnosing Sacroiliitis during the early onset of disease.

Can identify both inflammation and structural changes caused by inflammation.

Can be used to delineate the Enthesitis by detecting an inflammatory response that involve the soft tissue and underlying bone marrow at the area of Enthesis , using Fat-suppressed MRI technique.

Give the information about the changes of the synovial and cartilage Ability to differentiate between an active inflammatory axial disease and

non-inflammatory causes. Help in demonstrating the inflammation, bone marrow edema, and pre-

radiographic erosions in the sacroiliac joints. Even the MRI is considered as safe due to the use of magnetic wave, it is

high in cost. (Mager, Althoff, Sieper, Hamm & Hermann, 2009)

Nuclear Medicine has high in sensitivity, but quite low in specificity as it offers the functional imaging and able to identify any abnormalities that are not seen in other imaging modalities.

It is used to assess an active disease at the early onset of Ankylosing Spondylitis However, the role of this modality is still debatable since the nuclear medicine is

still growing and savvy. It is needed for continuing research on the efficiency of this modality (PET/ PET-CT/ PET-MR) for diagnosing the disease and the images need to compare with other modality’s images.

The study on 18F-fluoride PET/CT; quantified the uptake of the affected area by Standardized uptake value (SUV) is believed to be superior than bone scintigraphy (with tracer Tc99m MDP) and PET with tracer 18FDG as the overall sensitivity of PET/CT is 80% since the CT part of PET-CT provides an exact localization of active lesion as well as demonstration of chronic changes, for example erosions and usually, the PET-CT images need to compare with MRI’s images.

It is quite expensive and high in dosage compared to other modalities(Desai, Sriskanadan & Howlett, 2010)

The detection of sacroiliac joint changes in Ankylosing Spondylitis is believed more excellent in CT compared to conventional radiography

Help in encompass the joint erosions, changes of subchondral bone and better visualization of enthesitis.

Since the CT comes with varying software, for example, specific window width and window level, or other algorithms, it allows for better definition of bone detail, overlapping of soft tissue, intestinal loops and/ or air.

However, the limitation of CT is as it has higher dosage and quite expensive(Guglielmi, Scalzo, Cascavilla, Carotti, Salaffi, & Grassi, 2009)

Reveal the presence of Enthesitis clearly as compared to conventional radiography Used to monitor the changes of blood flow in the Enthesis area, in which the

increasing of blood flow indicates that there is an active inflammation. Musculoskeletal ultrasonography instead can only visualize the superficial part of

the SIJ It is a very cost efficient imaging technique, but it is less sensitive in the detection

of erosions (Eder, Barzilai, Peled, Gladman & Zisman, 2012)

6.0 - Image Features of Ankylosing spondylitis

in the Imaging Modalities

Conv

enti

onal

Rad

iogr

aphy

Classic Radiographic Hallmark : “Sacroiliitis”, which is the fusion of both Sacroiliac Joints with Lumbar spine Erosion of Bony SubchondralBony Subchondral Sclerosis and proliferation

(Berens, 1971; Resnick et al., 1977 as cited in Ostergaard & Lambert, 2012)

Symmetrical deformities of the sacroiliac joints in which the joints are becoming widen on the early onset but it becomes narrow and fused on the late onset of disease

(Desai et al. 2010)‘Shiny Corner’ / ‘Romanus Lesion’ appearance due to reactive sclerosisThe vertebral bodies become squared

(Herman et al, 2005 as cited in Ostergaard & Lambert, 2012)

‘Bamboo spine’ appearance that resulted from bony ossification and bony spur/ syndesmophytes formation were fused the vertebra

(Desai et al. 2010)

Mag

neti

c Re

sona

nce

Imag

ing

Sacroiliitis and spine bridging Subchondral bone marrow oedemaNarrowing of joint spacesPeriarticular fatty tissue accumulation

(Hermann & Bollow, 2004; Maksymowych & Landewe, 2006 as cited in Ostergaard & Lambert, 2012)

Bone erosions (defects in iliac surface on the early onset and sacral surface at later onset)Synovitis and joint effusion (hyperintensity within the joint)Capsulitis (STIR hyperintensity or capsule’s contrast enhancement and enthesitis (seen as junctional zone T2W hyperintensity)Subchondral fatty deposition (seen as subchondral T1W hyperintensity which gets suppressed on fat-saturated images.

(Daya , Shailesh & Aparna, 2014)

Nuc

lear

Med

icin

e (P

ET-

CT)

Sacroiliac JointsBone (iliac surface) erosionSubchondral bone changes (demineralization)Enthetitis

(Guglielmi et al. 2009)

Subchondral sclerosis

(Daya et al. 2014)

Complication of AS

Spinal fractureSpondylodiscitis

(Ostergaard & Lambert, 2012)

Com

pute

d To

mog

raph

y Visualization of multiple focal spot at the area of affected.Able to visualize the erosions, sclerosis and anklosingCT part of PET-CT provide an exact localization of active lesion

(Desai et al, 2010)

Ult

raso

nogr

aphy

The appearance of Enthesitis of ultrasonography images:

The tendon was appeared as thickened and hypoechogenicitCortical bone abnormalities (bone erosion, enthesophytes, Calcifications)Doppler signals

(Eder et al. 2012)

Conventional Radiography

Supplemental radiographs demonstrate syndesmophyte formation of the cervical spine as well as osseous bridging of the facet joints. Single view of the left knee demonstrates enthesopathic change along the course of the MCL

Early vertebral changes. Lateral radiograph of the lumbar spine in a 28-year-old man shows squaring of the vertebral bodies secondary to small osseous erosions at the corners (so-called “shiny corners”). Note the syndesmophyte formation at the anterior L4 to 5 disk space (arrow). (Adapted from

Diagnostic Imaging, 2013)

(Adapted from Mansour, Cheema, Naguwa, Greenspan, Borchers, Keen & Gershwin, 2007)

Conventional RadiographyFigure 1. Radiographic findings in

sacroiliac joints and spine in ankylosing spondylitis. (A) Radiograph of the sacroiliac joints in a 23-year old male demonstrates established ankylosing spondylitis. Bilateral erosions cause discrete foci of loss of subchondral bone and apparent joint space widening in some areas (arrows) and ill definition of the joint margin in other areas (arrowheads). Bilateral subchondral sclerosis is most prominent in the left ilium. (B)–(D) Radiographs of the spine in a 47-yearold male with widespread ankylosis. The cervical spine (B) exhibits extensive formation of vertical syndesmophytes that have bridged the anterior vertebral corners causing ankylosis. Some facet joints are fused, best appreciated at C2/3. The lumbar spine (C; enlargement of L1–L4 in D) shows similar ankylosis. Note the thick right L1/2 bridging (arrow) and compare this to the delicate vertical syndesmophytosis on the left at L3/4. The sacroiliac joints are completely fused with barely any remnant of joint visible.

(Adapted from Ostergaard & Lambert, 2012)

Magnetic Resonance Imaging

(Adapted from Mager et al. 2009)

45 years old patient with ankylosing spondylitis under infliximab therapy suffering from inflammatory back pain. Whole-body coronal T1-weighted (A) and whole spine sagittal STIR (B) sequences, magnifications of coronal sequences (box in A; C: T1-weighted; D: STIR) and sagittal sequences (box in B; E: T1-weighted; F: STIR). There is complete fusion of the sacroiliac joints (black arrows) without any inflammatory activity (D) as well as active anterior spondylitis (Romanus lesion) characterized by an erosion of the end plate of L5 (white arrow) and osteitis at the anterior corners of L4 and L5 (arrowheads), the attachment sites of the annulus fibrosus. A small degenerative tear of the posterior annulus fibrosus (small white arrow) and disc herniation is also seen.

Magnetic Resonance Imaging

(Adapted from Diagnostic Imaging, 2013)

Findings: (1) Sagittal sequences demonstrate syndesmophyte formation along the anterior vertebral column. There is also increased signal in the lower intervertebral discs on the T1 and T2 sequences which in this situation corresponds to calcification of the disc. (2) Coronal sequence demonstrates fusion of the sacroiliac joints and (3) the axial sequence demonstrates dural ectasia and thecal diverticula

21

3

45-year-old man with ankylosing spondylitis: postinflammatory fatty vertebral changes after Romanus spondylitis. Sagittal fast spin-echo T1-weighted image of thoracic spine shows circumscribed hyperintensity of anterior edges of vertebral endplates corresponding to fatty infiltration of bone marrow long after florid inflammatory Romanus spondylitis (arrows).

(Adapted from Lacout, Rousselin & pelage, 2007)

Computed Tomography

(1) CT scan (sagittal reformation) shows sclerotic changes and erosions of vertebral endplates (arrows) (2) Coronal CT scans of thoracic and lumbar spine show syndesmophytes corresponding to osseous bridge between two adjacent vertebrae (arrows)

53-year-old woman with ankylosing spondylitis: sacroiliac joint ankylosis. A and B, Axial CT scan (A) and volume reformation, frontal view (B) of sacroiliac joints show complete ankylosis with homogeneous osseous bridge passing through articulations (arrowheads).A B

21 (Adapted from Lacout et al. 2007)

Bone Scintigraphy

[18F]FDG and [18F]fluoride PET-CT and MRI images of one AS patient. Coronal PET (A, B) and PET-CT (B, D) images with [18F] FDG (A, B) and [18F]fluoride (C, D). Multiple hotspots are shown; an example is indicated by a red closed arrow (C). (E) Sagittal MRI short-tau inversion recovery (STIR) image of vertebral column. Multiple lesions with increased signal (bone marrow oedema) are shown; an example is indicated by the open arrow.

(Adapted from Van Der Laken, Huisman & Voskuyl, 2012)

Ultrasonography

Figure: (1) Lack of homogenous echotexture pattern, with loss of the tendon’s tightly packed echogenic lines and increased thickness of the Achilles tendon, (2) Positive power Doppler signal at the tibial tuberosity enthesis, (3) Posterior pole of calcenous erosion at the Achilles’ tendon enthesis, (4) Enthesophyte at the Achilles’ tendon enthesis.

43

21

(Adapted from Eder et al. 2012)

7.0 - REFERENCES

Daya, P. , Shailesh, M. P. & Aparna, I. , (2014, August). Seronegative Spondyloarthropathy-related sacroiliitis: CT, MRI features and differentials. Indian Journal of Radiology and Imaging, 24(3): 271-278

Desai, A. U. , Sriskanadan, N. & Howlett, D. C. (2010). Imaging of Musculoskeletal System. Orthopaedic Surgery., 28(10): 518-522

Diagnostic Imaging (2013, October 09). Ankylosing Spondylitis. Retrieved Oct 23, 2014 from http://www.diagnosticimaging.com/case-studies/ankylosing-spondylitis/page/0/2

Diagnostic Imaging (2013, October 09). Ankylosing Spondylitis. Retrieved Oct 23, 2014 from http://www.diagnosticimaging .com/case-studies/ankylosing-spondylitis/page/0/4

Diagnostic Imaging (2013, October 09). Ankylosing Spondylitis. Retrieved Oct 23, 2014 from http://www.diagnosticimaging.com/case-studies/ankylosing-spondylitis/page/0/7

Ebringer, A. 2013, Ankylosing Spondylitis and Klebsiella, [Online], Retrieved Oct 2, 2013 from books.google.com.my/books?id=Vxbjluhg7o0C&printsec=frontcover&dq=ankylosing+spondylitis+and+klebsiella&hl=en&sa=X&ei=LfNYUpriAcnZrQfSg4FQ&redir_esc=y#v=onepag e&q=pathogenesis%20of%20ankylosing%20spondylitis%20and%20klebsiella&f=fals

Eder, L., Barzilai, M., Peled, N., Gladman, D. D., Zisman, D. (2012, July 23). ‘The Use of Ultrasound for the Assessment of Enthesitis in Patients with Spondyloarthritis’. The Royal College of Radiologists, 68: 219-223

Ehrenfeld, M. (2012). Spondyloarthropathies. Best Practice & Research Clinical Rheumatology, 26: 135-45

Guglielmi, G. , Scalzo, G. , Cascavilla, A. , Carotti, M. , Salaffi, F. & Grassi, W. (2009, June 13). Imaging of the Sacroiliac Joint Involvement in Seronegative Spondylarthropathies. Clinical Rheumatology, 28:1007-1019

Healthwise, 2014. Ankylosing Spondylitis. Retrieved Nov 02, 2014 from https://myhealth.alberta.ca/health/pages/conditions.aspx?hwid=tr4496

Kowalczyk, N. & Mace, J. D. 2009, Radiographic Pathology for Technologists, 5th edn, Mosby Elsevier, United State

Lacout, A. , Rousselin, B. & Pelage, J. , (2008, October). CT and MRI of Spine and Sacroiliac Involvement in Spondyloarthropathy. American Roentgen Ray Society, 191: 1016-1023

Mager, A. , Althoff, C. E. , Sieper, J. , Hamm, B. , Hermann, K. A. (2009, April 15). Role of Whole-body Magnetic Resonance Imaging in Diagnosing Early Spondyloarthritis. European Journal of Radiology, 71: 182-188

Mansour, M. , Cheema, G. S. , Naguwa, S. M. , Greenspan, A. , Borchers, A. T. , Keen, C. L. & Gershwin, M. E. (2007). Ankylosing Spondylitis: A Contemporary Perspective on Diagnosis and Treatment. Semin Arthritis Rheum, 36: 210-223

Ostergaard, M. , Lambert, R. G. W. (2012). Imaging in Ankylosing Spondylitis. Therapeutic Advances in Musculoskeletal Disease, 4(4): 301-311

Porter, R. S. & Kaplan, J. L. (eds) 2013, The Merck Manual for Health Care Professionals: Ankylosing Spondylitis. Retrieved Oct 01, 2014 from: www.merckmanuals.com/professional/musculoskeletal_and_connective_tissue_disorde

rs/spondylitis.html?qt=ankylosing%20spondylitis&alt=sh

Spondylitis Association America, 2013. Ankylosing Spondylitis & Related Disease Information: Diagnosis, Symptoms, Treatment & More. Retrieved Nov 10, 2014 from http://www.spondylitis.org/about/as_sym.aspx

Van Der Laken, C. J. , Huisman, M. H. , Voskuyl, A. E. (2012). Nuclear Imaging of Rheumatic Disease. Best Practice & Research Rheumatology, 26: 787-804