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 SPONDYLİTİS AS

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, andAdolph Strümpell Pierre Marie of France in 1898Pierre Marie

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 0.2 - 0.86% –Male>female –About 90% of the patients express the HLA-B27 genotype. HLA-B27 –Tumor necrosis factor-alpha (TNF α) and IL-1 are also implicated in ankylosing spondylitis.Tumor necrosis factor-alpha IL-1

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 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

53. Imaging Magnetic resonance imaging (MRI) –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: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.Assistive devices

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.sulfasalazine

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.Etanercept Infliximab is an intravenous medicine that is injected into a vein.Infliximabintravenous 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 surgeryip 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)psoriasisarthritis 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. The goal of treatment for psoriatic arthritis is to control inflammation. Skin symptoms and joint symptoms are usually treated at the same time. Treatment

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 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.