1. Seronegative Spondyloarthropathies SpA
Prof. ECE AYDOĞ
Physical Medicine and Rehabilitation

2. Learning objectives:
1. be able to enumerate diseases in Spa group and describe common characteristics of Spa, differentiate diagnosis of inflammatory low back pain . 2.
be able to describe epidemiology and pathogenesis of ankylosing spondylitis
be able to enumerate articular and extraarticular finding of ankylosing spondylitis
be able to diagnose ankylosing spondylitis with the laboratory and imaging methods
be able to enumerate pharmacological and non pharmacological treatments of ankylosing spondylitis

3. Learning objectives:
3. be able to enumerate clinical types, poor prognostic criteria and pharmacological treatment approaches of psoriatic arthritis.
4. be able to enumerate clinical features, diagnostic and therapeutic approach of reactive arthritis and enteropathic arthritis.

4. Seronegative Spondylarthropathy Rheumatoid Factor is negative HLA B27 positive

5. HLA-B27 associated spondyloarthropathies
Ankylosing spondylitis
Undifferentiated spondyloarthopathy
Reactive arthritis
Arthritis associated with inflammatory bowel disease (IBD)
Psoriatic spondyloarthritis
Juvenile enthesitis-related arthropathy
Iritis

6. Common features of spondylarthropathies
Familial clustering
Association with HLA-B27
Axial joint involvement
Asymmetrical peripheral joint involvement
Enthesitis (the insertion of tensile connective tissue into bone).
Extra-articular signs
Negative rheumatoid factor

15. New Classification Criteria for SpA The Assessment of SpondyloArthritis International Society (ASAS, 2011)
(to be applied in patients with chronic
back pain ≥ 3 months and age at onset of back pain<45 years)
the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm")
or the presence of HLA-B27 plus at least two SpA features ("clinical arm")

16. SpA features Inflammatory back pain Arthritis Enthesitis (heel)
Uveitis
Dactylitis
Psoriasis
Crohn’s/colitis
Good response to NSAIDs
Family history for SpA
HLA-B27
Elevated CRP

17. ANKYLOSİNG SPONDYLİTİSAS

18. Clinical Picture

19. ankylos; bent spondylos; vertebrae
Ankylosing spondylitis (AS) from Greek
Bechterew's disease,
Bechterew syndrome,
Marie Strümpell disease
Vladimir Bechterew of Russia in 1893,
Adolph Strümpell of Germany in 1897, and
Pierre Marie of France in 1898

20. Ankylosing Spondylitis
Chronic, systemic inflammatory disorder of the axial skeleton
Sacroiliitis is hallmark of the disease
Spondylous-spine
Strong genetic predisposition (HLA-B27)

21. Ankylosing Spondylitis
Commonest of SPA
Prevalence %
Male>female
About 90% of the patients express the HLA-B27 genotype.
Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis.

22. Pathology Axial joints Large peripheral joints Entheses
Inflammation; in subchondral bone marrow
Reparation; development of chondroid metaplasia, followed by calcification of cartilage and formation of bone, particularly in the axial joints.

23. Pathology- Sacroiliac Joint
MRI reveals inflammation in the posteroinferior capsular region and subchondral bone of the synovial portion of the joint:
cellular infiltration with lymphocytes, macrophages, and plasma cells in the synovium and subchondral marrow as the earliest features of disease

24. Pathology-Sacroiliac Joint
Later features include the development of pannus extending from both synovium and subchondral bone marrow, with erosion of articular cartilage (widening of the joint space) and its replacement by granulation tissue

25. Pathology-Sacroiliac Joint
Reparative changes include cartilage metaplasia at sites of active inflammation, followed by its calcification and then replacement by endochondral bone, leading to obliteration of the joint space by ankylosis

26. Pathology-Spine
Chronic inflammation (lymphocytes, plasma cells, and macrophages) leads to resorption of bone (first observed in the outer annulus fibrosus, particularly at its insertion into the rim of the vertebral end plate )
This, followed by reparative changes in adjacent trabecular bone and bone apposition on the waist of the vertebral body during postinflammatory remodeling, accounting for the squaring and shining corner appearance on plain radiography

27. Pathology- Spine
Cartilage metaplasia of granulation tissue is followed by its calcification and then replacement by bone at the vertebral margin and in the outer annulus.
This extends across the vertical length of the disk, eventually leading to complete bony fusion of adjacent vertebrae and the appearance of a syndesmophyte on plain radiography.

29. Pathology-Spine
Extensive involvement of the entire spine results in the “bamboo spine” appearance on plain radiography.
The process of inflammation may also involve the central portion of the disk, which is best seen on MRI as spondylodiscitis.

30. Pathology- Spine Ankylosis in the adjacent intervertebral disk
Ankylosis in the apophyseal joints
Ankylosis in the adjacent intervertebral disk
Enthesitis:
Costotransverse and costovertebral joints
Supraspinous and intraspinous ligaments

31. Enthesitis Tenderness at : Achilles insertion Costochondral junctions
Ischial tuberosities

32. Skeletal manifestations
Back pain insidious in onset
First clinical manifestation in 75%

33. Skeletal manifestations
Pain early is quite severe and aggravated by coughing, sneezing or sudden twisting
Felt deep in gluteal region and hard to localize
Worsen after prolonged periods of inactivity

34. Skeletal manifestations
Chest pain
Costevertebral,
Costasternal,
Manubriosternal joints involvement
(Enthesopathy)

35. Skeletal manifestations
Extra-articular tenderness
(Enthesopathy)
Joints involvement
girdle or “root” joints (hips and shoulders) (up to %35)
knee joints,
temporomandibuler joints

36. Ankylosing Spondylitis Extra skeletal manifestations
Eye disease
Iritis %25-30
Cardiac abnormalities %3.5
Aortic valve imcompetence
Cardiac conduction disturbances
Pulmonary disease
Pulmonary apical fibrosis
Neurologic involvement
Spinal fracture, instability, compression, or inflam.
Atlantoaxial subluxation
Myelopathy
Cauda equina syndrome

37. Ankylosing Spondylitis Extra skeletal manifestations
Renal involvement
Ig A nephropathy
Microscopic hematuria
Proteinuria
Amyloidosis
Osteoporosis

38. Physical findings Spinal Mobility
Limitation of motion of the lumbar spine
Loss of normal lumbar lordosis

39. Modified Schober’s test of lumbar flexion

40. Physical findings Chest expansion Reduction below 5 cm
Level of the 4 . intercostal space in males, and just below the breasts in females.
The amount of chest expansion is measured from deep expiration to full inspiration.

41. Enthesitis Tenderness at : Achilles insertion Costochondral junctions
Ischial tuberosities

42. Sacroiliitis Sacroiliac pain is often found in the early stage of AS.
Gaenslen, Mennel, Thrust, Patrick (Faber) test
These maneuvers stresses the sacroiliac joints. Increased pain during these maneuvers could be indicative of joint disease.

43. Gaenslen, Thrust, Patrick (Faber) test

44. Physical findings Posture Limitation of nevk movements
Reduced occiput-wall distance or tragus-wall distance
Toracic kyphosis
Disese duration of 10 years or more

45. Occiput-wall distance or tragus-wall distance

46. Laboratory tests HLA B-27 + in majority of patients
Acute phase reactants
Mild increase Alk Phos
Mild anemia
Some elavation serum Ig A

47. Radiography Sacroiliitis: Modified New York Criteria 0 Normal
1 suspicous
2 minimal sacroiliitis
3 modarete sacroiliitis
4 ankylosis

49. Radiography Bony erosions and osteitis (“whiskering”)
Squaring of the vertebral bodies
Syndesmophytes
Bridging Syndesmophytes
Bamboo spine

51. Bamboo spine

53. Imaging Magnetic resonance imaging (MRI) Computed tomography (CT)
Demonstrate early stages of sacroiliitis
Computed tomography (CT)
for the detection of bone changes, such as
erosions, and ankylosis, CT can be superior to MRI imaging

54. Diagnosis Inflammatory back pain
Limitation of spinal movement in all planes
Early morning stiffness
Radiological evidence of sacroiliitis

55. Treatment Goals: Relieving pain and stiffness, Reducing inflammation,
Keeping the condition from getting worse,
Enabling you to continue daily activities.

56. Initial Treatment for AS
Education, so you know what you can expect as ankylosing spondylitis progresses and how you can minimize problems that can be caused by your condition

57. Ongoing treatment for AS
Exercises:
to maintain mobility and control pain,
to help maintain good posture,
to enhance lung capacity with deep breathing exercises
Physical therapy:
Heat and cold to help control pain and stiffness. Heat can help with relaxation and pain relief, and cold can help decrease inflammation.
Assistive devices such as canes or walkers, allow to maintain physical activity while reducing stress on joints.

59. There are different types of exercises that you can do to lessen your pain and stiffness:
Range of motion exercises reduce stiffness and keep your joints moving.
Strengthening exercises maintain or increase muscle strength.
Endurance exercises strengthen your heart, give you energy and control your weight. These exercises include things like walking, swimming and cycling.
Moderate stretching exercises help relieve the pain and keep the muscles and tendons around an affect joint flexible and strong. 

60. Medication for AS
Nonsteroidal anti-inlammatory drugs (NSAIDs): first recommendation to reduce pain and inflammation.
Disease-modifying antirheumatic drugs (DMARDs): may help relieve pain in joints other than the spine and pelvis. The DMARD most often studied and prescribed for ankylosing spondylitis is sulfasalazine, which is a combination of aspirin and an antibiotic.

61. Medication for AS
Drugs known as "biologic agents" or "anti-TNF-alpha" drugs reduce inflammation by blocking called tumor necrotizing factor (TNF) alpha that causes inflammation.
Etanercept is a medicine injected under the skin.
Infliximab is an intravenous medicine that is injected into a vein.
Adalimumab is a medicine injected under the skin.

62. Surgery Joint replacement surgery:
This is a surgical operation, where the affected joint is removed and replaced by suitable artificial joint structures. 
Hip replacement surgery
Lumbar spinal osteotomy: Is done to correct the permanently bent posture of persons in advanced stages of Ankylosing spondylitis

64. REACTİVE ARTHRİTİS

65. Reactive Arthritis Also known as Reiter’s syndrome
Named after Hans Reiter, a German Physician in 1916
Symptoms of arthritis, conjunctivitis, non gonococcal urethritis
Following bouts of bloody dysentery
> 75% HLA B27 positive

66. Reactive Arthritis
The classic triad of the disease, namely urethritis, arthritis, and conjunctivitis, is present in only one third of the patients.
Occurs 2-4 weeks after inciting infection
Most responsible organisms have an affinity for mucous membranes

67. Reactive Arthritis
Secondary immune reaction, in susceptible individuals, to primary infection:
Yersinia
Campylobacter
Shigella
Salmonella
Chlamydia

68. Urethritis First manifestation usually non gonococcal urethritis
Occurs in both venereal and non venereal forms of the disease
Males Fameles
Mucopurulent discharge Vaginal discharge
Dysuria Dysuria
Prostatitis Purulan cervicitis
Epididymitis

69. Conjunctivitis Follows urethritis by several days
Often mild and transient
- Acute anterior uveitis possible

70. Articular symptoms Typically appear last Additive, oligoarticular
Lower limbs most common
Recurrent attacks common in chlamydia-induced arthritis
Prognostic signs for chronicity
Hip/heel pain
High ESR
Family history and HLA-B27 +

71. Keratoderma blennorrhagicum

72. Circinate Balanitis

73. Glossitis/ Mucocutaneous Lesions

74. Gastrointestinal tract
Mild diarrhea; occ. it may be bloody and prolonged
During articuler clinical remission the inflammatory gut lesions disappeared

75. Hearth Conduction abnormalities Aortic regurgitasyon
Severe and long standing disease

76. Miscellaneous features
Ig A nephropathy
Amyloidosis
Neurologic complications
Peripheral neuropathies
Encephalopathy
Transverse myelitis
Thrombophelebitis
Purpura
Livedo reticularis

77. Differential diagnosis and investigation
Septic arthritis
Gout
Acute onset of other SpA
Raised ESR/CRP
Aspirate joint to exclude infection/crystals
Urethral swab, stool culture
Contact tracing if necessary

78. Clinical Course Normally limited course running 3-12 months
15% with prolonged relapsing arthritis
20 % patients will have chronic arthritis, which is usually mild
A small percentage of patients will have deforming arthritis
Ankylosing Spondylitis in 10% of cases

79. Laboratory Findings Normochromic, normocytic anemia Leukocytosis
Acute phase reactants:
ESR
C-reactive Protein
- HLA-B27 positive 75%
- Synovial fluid- highly inflammatory
- Sterile cultures - negative gram stain

80. X-Ray
X-Ray reveals periostitis with eventual new bone growth

81. Treatment NSAIDS Local glucocorticoids enjection
Systemic glucocorticoids (rare)
Uveitis-glucocorticoids
DMARDS
Sulfasalazine
Methotrexate
Antimicrobial drugs are not indicated in SPA in the absence of infections

82. PSORIATIC ARTHRITIS
PsA

83. Psoriatic arthritis
PsA is a chronic disease characterized by inflammation of the skin (psoriasis) and joints (arthritis)
Psoriasis causes a scaly skin rash on the elbows, knees and scalp and swelling and pain in joints 
Usually affects the wrists, knees, ankles, fingers and toes. It can also affect the back.

84. How common is psoriatic arthritis?
Affects men and women in equal numbers
Appears in people between the ages of 20 and 50
Up to 30% of people with psoriasis also get psoriatic arthritis
Although psoriasis may start at any age (commonly in the late teens), the arthritis component usually makes its appearance later - in the 20s, 30s and 40s
In a small percentage of people (approximately 15%), arthritis may show first

85. What are the warning signs of psoriatic arthritis?
Pain and swelling on the joints
Pain and swelling over tendons
ligaments
Tenosynovitis
Enthesitis
Dactilitis (sausage digit)
Morning stiffness
Finger nails or toe nails lifting up from the skin or getting small holes in them (known as pitting)

86. Psoriatic arthropathy clinical forms
1-Oligoarticular (70%) • Asymmetric
2.Asymmetric DIP form
3.Arthritis mutilans (5%) • Osteolysis of fingers
4.Symmetric polyarthritis (15%) • RA, RF –
5.Psoriatic spondylarthritis (5%) • SPA, 40-60% HLA-B27 +

89. Laboratory There is no diagnostic laboratory test ESR % 40-60
Low titers RF % 5-16
Low titers antinuclear outoantibodies %2-16

90. Diagnosis Modified ESSG criteria for psoriatic arthritis
Inflammatory spinal pain or
Synovitis (either asymmetrical or predominantly lower limb)
and
One or more of the following:
Positive family history of psoriasis
Psoriasis

91. Poor Prognosis Extensive skin involvement
A strong family history of psoriasis
Female gender
Disease onset at <20 years of age
Expression of HLA-B27, -DR3 or -DR4 alleles
Polyarticular or erosive disease

92. Treatment
The goal of treatment for psoriatic arthritis is to control inflammation.
Skin symptoms and joint symptoms are usually treated at the same time.

94. ENTEROPATHIC ATHRITIS

95. Enteropathic arthritis
Inflammatory bowel disease (IBD)
Ulcerative colitis
Crohn's disease
About one in five people with Crohn's or ulcerative colitis will develop enteropathic arthritis.

96. Causes of Enteropathic Arthritis
Many people don't realize that the gastrointestinal tract contains the largest immune system in the body
The immune system is the body's natural defense against foreign invaders, and it is somehow altered in people who have these conditions
Some researchers believe that the long-lasting inflammation found in the intestines of people with IBD damages the bowel, which in turn may allow bacteria to enter the damaged bowel wall and circulate through the blood stream
The body's reaction to these bacteria may cause other problems including inflammation in the joints and/or spine, skin sores and inflammation of the eyes

97. Symptoms IBD Symptoms Abdominal pain Arthritis Symptoms
Bloody diarrhea
Arthritis Symptoms
One or more peripheral (limb) joints such as an arm or leg, although the lower limbs are more commonly affected
Arthritis symptoms may precede the IBD symptoms

98. Symptoms
The severity of the peripheral arthritis normally coincides with the severity of the IBD
About one in six people with IBD also has spinal inflammation, although this inflammation is independent of the severity of the bowel disease symptoms

99. Diagnosis Medical history Stool culture
Colonoscopy with or without bowel biopsies
ESR, CRP level
HLA B27
Synovial fluid analysis
X-rays

100. Disease Course/Prognosis
The course and severity of enteropathic arthritis varies from person to person
The disease "flares" - the times when the disease is most active and inflammation is occurring - tend to be self-limiting, often subsiding after 6 weeks, but reoccurrences are common
In some cases the arthritis may become chronic and destructive

101. Treatment NSAIDs Sulfasalazine
Joint swelling
Intestinal lesions
Less helpful in treating arthritis of the spine
Biologic medications, the TNF inhibitors, have shown great promise in treating spondylitis.