1. Ankylosing Spondylitis and Related Spondyloarthropathies3

2. Spondylarthropathy Association with HLA-B27 Inflammatory back pain
Sacroiliitis
Enthesitis
Common extral -articular manifestation

3. AS Pathogenesis Genetic: B27
Multifactorial: genetic and environmental
Genetic: B27
AS develops in 2–5% of HLA–B27-positive individuals.
First-degree relatives HLA-B27–positive ≈15-20% chance of developing AS,10 times more than B27-positive individuals with no such family history
HLA-B27 chromosome 6 most polymorphic present in all cells except mature erythrocytes and trophopastes directly involved as disease severity &/or susceptibility gene. additional disease predisposing genes

4. AS Pathogenesis
Environmental:
Bacterial triggers: Molecular mimicry

5. Enthesitis
Enthesis as the area of insertion of tendon, ligament, joint capsule, or fascia to bone
Hallmark that characterized SpAs
Enthesis is not a static one.
-high capacity for dynamic tissue turnover in continual response to changes in mechanical factors.
This would explain why this is a target for inflammation.

6. Enthesitis . There are 2 types:
Fibrous entheses :dense fibrous connective tissues linking tendon and ligament to bone. located at the metaphyses and diaphyses of long bones
Fibrocartilage entheses :more common, have an additional transitional zone of fibrocartilage at the bony interface located at sites with a great deal of joint movement, probably because fibrocartilage can dissipate mechanical stress.

7. Fibrocartilage enthesis of human Achilles tendon58
sesamoid
fibrocartilage
retrocalcaneal bursa
Enthesis
fibrocartilage
periosteal
fibrocartilage

8. History Vertebral symptoms. Inflammatory back Alternating buttock pain
first manifestation in 75% of patients.
Onset insidious occurring over months or years, at least 3 months.
Alternating buttock pain
Systemic features.
Morning stiffness characteristic.
Fatigue is common.
Fever and weight loss may occur during periods of active disease.
inflammatory back pain Most common symptom ,first manifestation in 75% of patients.
Onset insidious occurring over months or years, at least 3 months.
Morning stiffness lasting at least 30 minutes, improvement of symptoms with moderate physical activity.
Diffuse nonspecific radiation of pain into both buttocks.
Patients often experience stiffness and pain that awakens them in the early morning hours, a distinctive symptom not generally found in patients with mechanical back pain.
Most patients have mild chronic disease or intermittent flares with periods of remission.
The spinal disease rarely is active persistently.
The spinal disease starts in the sacroiliac joints.

9. History Non-vertebral Symptoms.
Asymmetric peripheral arthritis. Arthritis of the toe IP Joints. Sausage Digits. Achilis Tenosynovitis. Plantar Faciitis. Costochondritis. Iritis. Mucocutaneous Lesions
inflammatory back pain Most common symptom ,first manifestation in 75% of patients.
Onset insidious occurring over months or years, at least 3 months.
Morning stiffness lasting at least 30 minutes, improvement of symptoms with moderate physical activity.
Diffuse nonspecific radiation of pain into both buttocks.
Patients often experience stiffness and pain that awakens them in the early morning hours, a distinctive symptom not generally found in patients with mechanical back pain.
Most patients have mild chronic disease or intermittent flares with periods of remission.
The spinal disease rarely is active persistently.
The spinal disease starts in the sacroiliac joints.

10. Inflammatory back pain.
Most common symptom ,first manifestation in 75% of patients.
Onset insidious occurring over months or years, at least 3 months.
Morning stiffness lasting at least 30 minutes, improvement of symptoms with moderate physical activity.
Diffuse nonspecific radiation of pain into both buttocks.
Patients often experience stiffness and pain that awakens them in the early morning hours, a distinctive symptom not generally found in patients with mechanical back pain.
Most patients have mild chronic disease or intermittent flares with periods of remission.
The spinal disease rarely is active persistently.
The spinal disease starts in the sacroiliac joints.

11. Diagnosis of SpAs
Inflammatory back pain and at least two of the following.
Psoriasis.
Family history.
Response to NSIADs
Enthesistis.
Alternating buttock pain.
Peripheral arthritis.
Dactylitis.
Anterior uveitis.
Positive predictive probability >90% for diagnosis of SpA

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16. insidious onset of chronic low back pain and stiffness
Early symptoms and progression of ankylosing spondylitis (AS). A, The characteristic early symptom is insidious onset of chronic low back pain and stiffness, beginning usually in late adolescence or early adulthood (mean age of onset, 24 years). The pain due to sacroiliitis is dull in character, difficult to localize, and felt somewhere deep in the gluteal region. It may be unilateral or intermittent at first; however, within a few months it generally becomes persistent and bilateral, and the lower lumbar spine area also becomes painful. Sometimes pain in the lumbar area may be the initial presentation. The symptoms typically worsen with prolonged inactivity or on waking up in the morning ("morning stiffness"), and improve with physical activity and a hot shower. The back pain and stiffness may awaken some patients from sleep and some may experience considerable difficulty in getting out of bed in the morning. Others may find it necessary to wake up at night to move about or exercise for a few minutes before returning to bed. Some patients may complain of easy fatiguability, perhaps resulting, in part, from their disturbed sleep pattern. B, Progression of AS over a period of 26 years; the patient underwent bilateral total hip arthroplasties in (B from Little et al. [82]; with permission.) Sites of inflammation. The inflammation primarily affects the axial skeleton and appears to originate in ligamentous and capsular sites of attachment to bones (enthesitis), juxta-articular ligamentous structures, and the synovium, articular cartilage, and subchondral bones of involved joints [19],[20],[21],[40],[41]. The site of enthesitis is infiltrated by lymphocytes, plasma cells, and polymorphonuclear cells; edema and infiltration of the adjacent marrow space are present. A striking feature is a high frequency of axial enthesitis and synovitis that can result in fibrous and later bony ankylosis of the sacroiliac joints and the spine [45]. Extra-articular or juxta-articular bony tenderness due to enthesitis at costosternal junctions, spinous processes, iliac crests, ischial tuberosities, or heels (arrows) may be an early feature of the disease. Stiffness and pain in the cervical spine and tenderness of the spinous processes may occur in early stages of the disease in some patients, but generally this tends to occur after some years. Back symptoms may be absent or very mild in an occasional patient, whereas others may complain only of back stiffness, fleeting muscle aches, or musculotendinous tender spots. These symptoms may be worsened on exposure to cold or dampness, and such patients may occasionally be misdiagnosed as having fibrositis (fibromyalgia). Some may have mild constitutional symptoms such as anorexia, malaise, or mild fever in early disease, and this may be more common among patients with juvenile onset, especially in developing countries. Involvement of the costovertebral and the costotransverse joints and occurrence of enthesitis at costosternal areas may cause chest pain that may be accentuated on coughing or sneezing. Some patients may note their inability to fully expand their chest on inspiration, but moderate to severe pulmonary restriction mostly occurs after long-standing disease.
Sites of inflammation

17. Schober's test

18. H and I, Test for eliciting sacroiliac pain by putting physical stress on the sacroiliac joints by application of downward pressure on the flexed knee, when the hip joint is flexed, abducted, and externally rotated; or by compression of the pelvis with the patient lying on one side (H). Two other procedures involve the application of direct pressure on anterior superior iliac spines, along with attempts to force them laterally apart, away from each other; and by forced flexion of one hip joint maximally toward the opposite shoulder, with hyperextension of the contralateral hip joint (I).

21. AS bilateral sacroiliitis grade III.
Sieper, J et al. Ann Rheum Dis 2002;61:8iii-18iii
Copyright ©2002 BMJ Publishing Group Ltd.

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26. Early radiographic signs include squaring of the vertebral bodies caused by erosions of the superior and inferior margins of these bodies, resulting in loss of the normal concave contour of the anterior surface of the vertebral bodies.
Inflammatory lesions at vertebral entheses may result in sclerosis of the superior and inferior margins of the vertebral bodies, called shiny corners (Romanus lesion).
Syndesmophytes :Ossification of the annulus fibrosus.
Over time, development of continuous (bridging) syndesmophytes may result in a bamboo spine, which, essentially, is fused. Spondylitis of AS starts in the lumbar or thoracolumbar spine and progresses proximally in a continuous fashion.
Radiographic signs are due to enthesitis, particularly Ossification of the annulus fibrosus results in fusion of the spine (bamboo spine).

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29. Metabolic bone disease Osteopenia:- increased risk of fracture. 58
Metabolic bone disease
Osteopenia:- increased risk of fracture.
Standard radiographs may not be revealing.
CT scan ,MRI may be required to aid in diagnosis.

30. Enthesitis

31. Potential Skeletal Sites of Inflammation of AS11
Inflammation primarily affects the sacroiliac joints and axial skeleton
Juxta-articular bony tenderness resulting from enthesitis at costosternal junctions,, spinous processes, lateral epicondyle, distal ulna, distal scapula, iliac crests, greater femoral trochanters, tibial tuberosities superior and inferior poles of the patella ischial tuberosity, insertion of the plantar fascia on the calcaneus or the metatarsal heads, the base of the fifth metatarsal head Achilles tendon insertion

32. Potential Other Disease Manifestations in AS12
Eyes
(Acute Anterior Uveitis)
Lungs
(Restrictive Lung Disease,
Apical Fibrocystic Disease)
Heart
(Aortic Insufficiency, Heart Block)
Kidneys
(Amyloidosis)
Gut
(Inflammatory Bowel Disease,
Microscopic Inflammatory Lesion)
Skin
(Psoriasis & Nail Changes)
Dactylitis
Cauda Equina Syndrome
Osteopenia

33. Ankylosing Spondylitis Differentiating Inflammatory vs Mechanical Back Pain
Courtesy of J. Cush, MD

34. AS in Women AS is approximately 3 times less common in women16
AS is approximately 3 times less common in women
The overall pattern of clinical disease is similar in both sexes; axial spinal disease more often may be milder in women than in men
However, self-ratings of pain and impairment of daily activities by women tend to show a less favorable overall outcome than in male patients
1. Kidd et al. J Rheumatol 1998; 15:1407-9
2. Carbonne et al. Arthritis Rheum 1992; 35:1479
3. Zink et al. J Rheumatol 2000; 27:613-22
4. Boonen et al. J Rheumatol 2001: 28:

35. Lab Studies. No laboratory tests are specific for AS.
Diagnosis is made by combining clinical criteria of inflammatory back pain and enthesitis or arthritis with radiological findings.
Anemia of chronic disease 15% of patients.
ESR or C-RP elevated in 75%..
Alkaline phosphatase is elevated in 50% patients
Serum IgA level may be elevated.
HLA-B27 positivity is present in 92% of white with AS .
Determining HLA-B27 status is not a necessary part of the clinical evaluation. 58

36. AS Yesterday: Severe Disease Outcome56
Obliteration of lumbar lordosis with atrophy of buttocks
Accentuation of thoracic kyphosis
Forward stoop of neck if the cervical spine is involved
Hip involvement can lead to
Flexion contractures
Compensated for by knee flexion
After hip
replacement

37. Management of AS NO smoking (significant negative impact on AS).
AS:- often misdiagnosed or diagnosed late ,under-treated
consider when seeing a young patient who has chronic back pain.
Basic therapy
Regular exercise .
Maintain posture.
NSAIDs
NO smoking (significant negative impact on AS).
Avoid physical trauma :-risk of fracture
Early diagnosis early introduction of biologic therapy is an important therapeutic goal
Anti-TNF-a therapy

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47. Previously healthy persons.
Reactive Arthrits :-
Sterile joint inflammation triggered by a distant infection
Weaknesses.
1-Bacterial components—may be detectable at the sites of inflammation.
A more appropriate definition would therefore be a joint inflammation triggered by a distant infection, with no cultivable microbes in the joints.
2-The disease is not limited only to the joints but affects the whole individual,
causing a variety of lesions.
Previously healthy persons.
• Triggering infection may pass unnoticed.
• Microbiological and serological investigations are the cornerstones of the diagnosis •.

48. Bacterial Infections that can Trigger HLA-B27-Associated Reactive Arthritis
Gastointestinal Infection a. Usual triggers:
 Shigella flexneri
 Salmonella enteritides and S. typhimurium
 Yersinia enterocolitica and Y. pseudotuberculosis
 Campylobacter jejuni
b. Unusual triggers:
 Shigella sonnei and S. dysenteriae
 Salmonella paratyphi
 Bacillus Calmette-Guerin
 Clostridium dificille
Urogenital Infection
a. Usual triggers:
 Chlamydia trachomatis
b. Unusual triggers:
 Ureaplasmaurealyticum.
Respiratoroy infection
 Chlamydia pneumoniae

49. Psoriatic Arthritis: Clinical Charactrastics
Erosive Arthritis
Arthritis in DIPs
Asymetric Arthritis Paravertebral Ossification and Sacroiliitis
Enthesopathy
Sausage Digits Nail Pitting or Onycholysis No Rheumatoid Nodules RF Negative

50. Epidemiology 5-7% are affected by an inflammatory arthritis.
Approximately 2% of the Caucasian population has psoriasis.
5-7% are affected by an inflammatory arthritis.
men and women are affected with equal frequency
The peak incidence 4th through 6th decades.

51. Clinical Manifestation
1. Asymmetrical mono- and oligoarticular arthritis (30-50% of cases)
2. Symmetrical polyarticular arthritis (30-50% of cases).
3. Distal interphalangeal (DIP) joint involvement (25% of cases) is nearly always associated with nail manifestations).
4. Arthritis mutilans (5% of cases) is characterized by resorption of the phalangeal bones.
5. Axial arthritis (30-35% of cases) may be different in character from ankylosing spondylitis,. It may present as sacro-iliitis, which may be asymmetrical and asymptomatic, or spondylitis, which may occur without sacro-iliitis and may affect any level of the spine in “skip” fashion.

52. Distinguishing PsA and RA
Enthesopathic features
dactylitis
enthesitis
Signs of psoriatic skin disease or nail disease
Spinal involvement or sacroiliitis

53. Distal interphalangeal (DIP) joint involvement (25% of cases) is nearly always associated with nail manifestations

54. Symmetrical polyarticular arthritis (30-50%).

55. Dactylitis presents as the so-called “sausage digit”, diffuse swelling of the entire digit likely due to a combination of both arthritis and tenosynovitis

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60. Nail involvement may be manifested as pitting, ridging, separation from the nail bed (onycholysis

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62. Extra-cutaneous manifestations
Conjunctivitis.
Uveitis.
Aortic insufficiency.
Pulmonary fibrosis.

63. Pencil-in-cup

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65. Sacroiliitis

66. Spondylitis,enthesitis and periostitis

67. Axial arthritis (30-35% of cases) may be different in character from ankylosing spondylitis,. It may present as sacro-iliitis, which may be asymmetrical and asymptomatic, or spondylitis, which may occur without sacro-iliitis and may affect any level of the spine in “skip” fashion.

68. Arthritis mutilans (5% of cases) characterized by resorption of the phalangeal bones.

69. Treatment
Treatment for psoriasis remains suppressive, rather than curative.
Articular disease .
Non-steroidal anti-inflammatory agents (NSAIDs).
patients with aggressive and potentially destructive disease, disease-modifying anti-rheumatic drugs (DMARDs) should be added early on in the course.
Methotrexate.is effective for both the cutaneous and peripheral articular manifestations of psoriasis. It is generally the first choice of DMARD, given its efficacy and tolerability.