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(Seronegative arthritis)
DR. PRUTHVIRAJ NISTANE
Post-Graduate student
Deptt. Of Orthopaedics,
Govt. Medical College and
Ra...
Objectives
 Gain a basic understanding of the Spondylo-
Arthritis
 Learn specific Characteristics of SpA
 Differentiate...
Introduction
 Are a diverse group of chronic, systemic
inflammatory conditions linked by
distinctive clinical, radiograph...
Introduction
 Absence of Rheumatoid Factor or other
autoantibody serologic abnormalities
 includes
○Ankylosing Spondylit...
ESSG (Europian SpA Study
Group)Criteria for diagnosis of
spondyloarthropathy
 Inflammatory spinal pain or synovitis (asym...
RA SpA
• UE>LE
• Often polyarticular
• Sacroiliitis absent
• RF usually pos
• No HLA-B27 assoc
• Sicca, scleritis
• LE>UE
...
Confusion
Can often see peripheral joint symptoms in
the absence of spinal symptoms
Pathology
 immune
 The pathology of spondyloarthropathies is
very different from that of RA. In RA, it is
the synovitis ...
Pathology
Osteitis follows
reactive bone sclerosis and
bone absorption, but then
more bone remodeling sets in
and it goe...
Pathology
 In RA, the cytokines lead to excessive
osteoclastic activity resulting in bone erosions,
 In spondyloarthriti...
Hallmarks
Inflammatory back pain (IBP)
Enthesitis - inflammation at sites where
tendons, ligaments, and joint capsule
fi...
Inflammatory Back Pain
 Worse in the late night and early morning
 Pain interferes with sleep to the point that the
pati...
Inflammatory Back Pain
 Exercise alleviates the pain rest makes it
worse.
 Affects younger patients
 Peaking during the...
Spondyloarthropathies
IBP persists for at least 3 months.
detrimental effects on quality of life
 increased disability,...
Spondyloarthropathies
 Also associated with osteoporosis and low bone
mineral density
 Ectopic bone formation occurs wit...
Clinical course
 The spine in the patient with AS fuses through:
 ligamentous ossification and
 syndesmophytosis,
 Rig...
Spondyloarthropathies
 Altered spinal biomechanics
 Combined with the brittle quality of the
osteoporotic bone
 Increas...
Sagittal reformatted CT scan showing a highly displaced
thoracic fracture. Asterisk indicates apposition of the
caudal fra...
Extra-articular
manifestations
 psoriasis,
 anterior uveitis,
 IBD,
 as well as rarer cardiac, renal, and
pulmonary ma...
Ocular Manifestations
 Uveitis is one of the most common
 occurring in 25% to 40% of patients.
 there appears to be no ...
Ocular Manifestations
 Presents as acute unilateral pain and photophobia
 Blurring of vision may also occur.
 Cataracts...
Cutaneous
Manifestations
 Plaque psoriasis
 Characterized by scaly,
erythematous, hyperkeratotic lesions
 most common f...
Cutaneous Manifestations
 assessment of less
conspicuous areas
including
 gluteal cleft
 scalp
 scalp line
 groin
 p...
Nail Changes
 Diffuse and numerous nail pitting (plate
depressions)
 Onicholysis (separation of the nail from
underlying...
Nail Pitting
Onicholysis toe nails
Crumbling nail/DIP joint involvement
Other Extra- articular Manifestations
 Apical pulmonary fibrosis : mostly asymptomatic
and typically observed in patients...
Gene association
 Up to 70% of individuals suffering from
SpA carry the HLA-B27 gene
 Strength of the association betwee...
Associations with HLA-B27
Rheumatic diseases
Ankylosing spondylitis
Reiter’s syndrome/reactive
arthritis
IBD related arthr...
(MARIE-STRUMPELL DISEASE)
(BECHTEREW DISEASE)
 A chronic, progressively inflammatory
disease of the spine and axial joints leading
to fibrous or bony ankylosis and def...
Etiology
 Not completely understood
 Auto-immune
 HLA-B27 : seen in 90 % patients
 Autosomal inheritance with 70 %
pen...
Pathology
 Most striking feature - high degree of fibrosis,
bony ankylosis, and inflammation that focus
on bone, cartilag...
Gross Pathology
 Start from SI joint
 Destruction of cartilage and articular cortex
 Fibrous or bony bridging
 Para-ar...
HistoPathology
Inflammatory cells in
ligamentous and periosteal area
Subchondral marrow oedema
Pannus and new bone formati...
Clinical features
 Insidious onset
 Begins in the Sacroiliac Joints –
 backache and morning stiffness
 radiation
 U/L...
Axial joints(a poor prognostic )
 Shoulders
 Hips
 Knees
Painful,swollon,
effusion,
muscle spasms
Flexion,
adduction
de...
Peripheral joints
 Osteoporosis
 Blurring of margins
 Joint space narrowing
 Bony ankylosis
• Kyphosis
• Loss of spina...
Systemic features
 Fatigue
 Weight loss
 Anorexia
 Night sweats
 Anemia
Diagnosis
Modified New York criteria (1984)
1. Limited lumbar motion
2. Low back pain for 3 months improved with exercise
...
Juvenile Ankylosing Spondylitis
Onset 8 to 14
Sex Ratio M:F 7 to 1
HLA-B27 91 %
Systemic symptoms rare
Polyarticular 97%
P...
Physical Examination
 Loss of spinal mobility
 Para spinal spasm
Spinal Involvement
 Tenderness – SI joints
 SI Compression Testing
 Modified Schober Test
 Potentially useful diagnost...
•Occiput to Wall distance
•Chest Expansion
 at the xiphisternum
 Normally > 5 cm
 Measurement is age and sex
dependant
...
Spinal Involvement
 Finger Tip to Floor Distance
 Measure fingertips to floor
 Useful for following patients over time
...
Radiological features
 Within 3 to 6 months
 SI joints – earliest
 Patchy osteoporosis
 Margins ill defined
 Widened
...
Sacroiliitis grading
0-normal
1-possible
2-minimal
3-moderate
4-ankylosing
The Spine
 Sharp squaring of anterior portion of
vertebral body
 Loss of concavity
 Loss of lardosis
 Subluxation of a...
•The reparative process forms
vertical linear bone ossification
along the outer fibers of the
annulus fibrosus of the disc...
MRI – Early changes
Progression and complications
Early stage(inflammatory)
 Intermittent, low-grade fever
 Fatigue
 Anorexia
 Sacroilitis...
Advanced stage(ankylosis)
 Constant low back pain
 Ankylosis , decreased ROM
 Muscle wasting in shoulder and pelvic gir...
Complications
 Fractures - Stiff osteoporotic spine is prone to
fracture and minor trauma. Most common
site of fracture i...
 Spinal stenosis – rare ; Result of bony
overgrowth of the spinal ligament and
facet joint.Symptoms are pain and
numbness...
Associated symptoms
 Aortitis
 Aortic dilatation
 Aortic regurgitation – scar tissue in aortic
valves
 Conduction abno...
Laboratory Investigations
• Elevated ESR/CRP
 HLA-B27 - found in 90-95% of patients
( 6% of general population)
• Synovia...
Differential diagnosis
 Ankylosing form of RA
 Other spondyloarthropathies
 Other causes of LBA
 Ochronosis
 DISH
Treatment - Goals
 Rehabilitation.
 Initiated before the disease fuses the
vertebrae and involves other organ.
 Directe...
Conservative management
 Corticosteroids – reduces inflammation
and relieves pain may overcome
deformity to some extent
...
Latest revolution
 Anti TNF-α therapy
Infliximab
Etanercept
 Rapid, profound and sustained response to
all aspects of di...
Posture and exercise
 Recumbence
 Hyperextension , abduction
 Deep breathing exercises
 Traction to lower extremities ...
Surgical management
 To relieve from disabling deformities
Total hip replacement
 Neck osteotomy and head removed
piecem...
Spinal osteotomy
Done at L2-3 or L3-4 level
Wedge of posterior spinal
column excised and
straightening of spine done.
M...
Thank you
(Seronegative arthritis)
II
Moderated by - Dr. K. S. Sandhu
Presented by - Dr. Pruthviraj Nistane
“Recap”
 Are a diverse group of chronic, systemic
inflammatory conditions linked by
distinctive clinical, radiographic, a...
ESSG (Europian SpA Study
Group)Criteria for diagnosis of
spondyloarthropathy
 Inflammatory spinal pain or synovitis (asym...
Hallmarks
 Immune mediated enthesitis and other
changes
 IBP
 Extra-skeletal manifestations
 Association with HLA – B27
ANKYLOSING
SPONDYLITIS
 PROTOTYPE
 Most common
 Crippling disease affecting young population
 Inflammatory back pain
...
(Reiter’s syndrome)
What is it ???
 Acute non-purulent arthritis complicating
an infection elsewhere in body
 Clinical syndrome triggered by...
“Reactive”
 viable micro-organisms do not enter the
joints and synovial fluid cultures are thus
negative.
 There is no u...
 Reiter’s syndrome –old aponym for reactive
arthritis
 clinical triad of arthritis, urethritis and
conjunctivitis.
 Rea...
Epidemiology
 age - is 18–40 years
 gender ratio in ReA following enteric infection is
nearly 1:1, whereas venereally ac...
Triggering infections
• Reactive arthritis is an arthritis induced by one of
the following bacteria:
 Urogenital:
• Chlam...
 Form of post infection arthritis that share
same clinical features as SpA.
 Whereas arthritis caused by or related to
o...
Pathology
• Synovial histology - is similar to that of other SpA
• Enthesitis - increased vascularity
Macrophage infiltrat...
Pathogenesis
Bacterias
• produce lipopolysaccharide (LPS)
• capacity to attack mucosal surfaces,
• survive intracellularly...
confusion ????
• Antigens from these bacterias have
been shown to be present in the
synovium and/or synovial fluid
leukocy...
Clinical picture
 Usually there is a delay of 1-4 wks from
infection till start of arthritis
 ranges from an isolated, t...
Musculoskeletal symptoms
Peripheral
• Typically there is asymmetric additive, oligoarthritis,
mainly of Lower limbs.
• Mos...
Axial
• Inflammatory low back pain
o Acute sacroiliitis
o insertional inflammation,
o muscle spasm
o arthritis in interver...
Extra-articular features in ReA
Mucocutaneous
• Keratoderma Blennorrhagica (20%)
palms and soles
• Circinate balantitis (3...
Pustules KB
Keratoderma
Blenorrhagicum
Urogenital lesions
males
• urethritis
• Prostatitis
females
• Cervicitis
• salpingitis
Ocular
• Conjunctivitis (60%)
• Uve...
Constitutional symptoms
 Fatigue
 Malaise
 Fever
 Weight loss
 Cardiac conduction defects
 Aortic insufficiency
 Ce...
Diagnostic Criteria
• Seronegative asymmetric arthropathy
and at least 1 of the following:
• Urethritis or cervicitis
• Di...
Prognosis
 Persists 3–5 months, but courses up to 1 year
can occur.
 Chronic joint symptoms persist in about 15% of
pati...
Laboratory investigations
Demonsration of the urogenital tract or bowel
infections
 During the acute phase:
• urine cultu...
 inflammatory arthritis:
• ↑ESR, CRP
• leucocytosis
• Synovial fluid analysis and culture
 HLA B27 (especially in chroni...
Differintial diagnosis
 Disseminated gonococcal
disease
 psoriatic arthropathy
 Other spondyloarthropathies
Treatment
 Eradicate triggering infection (antibiotics)
 Treat extra-articular manifestations:
Topical steroid
Uveitis...
1. NSAIDs: in full doses
Indomethacin, 75–150 mg/d in divided doses is the initial
treatment of choice
2. Local steroids i...
PSORIATIC
ARTHRITIS
What is it ???
 Psoriatic arthritis (PsA) refers to an
inflammatory arthritis that
characteristically occurs in individua...
Who Gets Psoriatic
Arthritis?
 Age of onset - 30-50 years
 1-3% of the population has psoriasis
 5 – 10 % of people wit...
Pathology
 shares pathogenic mechanisms with psoriasis
 immune-mediated
 Infiltration with T cells, B cells, macrophage...
Pathology
 synovial overexpression of proinflammatory
cytokines
• Interleukin 2
• Interferon
• TNF
 marked increase in o...
Clinical Features
 Psoriasis present before the onset of joint disease
(70%)
 Psoriasis comes with the arthritis (15%)
...
Confusion
Psoriatic Arthritis is a heterogenous disease
which can present in a multitude of ways
Wright and Moll Classification
(1) Arthritis of the DIP joints; 15 %
(2) Asymmetric oligoarthritis; 30 %
(3) Symmetric pol...
Arthritis of the DIP joints
Arthritis of the DIP joints
Asymmetric oligoarthritis
Asymmetric oligoarthritis
Symmetric polyarthritis
Axial involvement
Arthritis Mutilans
Arthritis Mutilans
Presentation
 Typical presentation is a peripheral inflammatory joint
disease – usually a mono or oligo arthritis
 Knees...
Progression -- later stages
 Sacroiliac Involvement
 Sacroiliitis in 1/3 of patients
 Usually asymmetric (unilateral)
...
Other features
 Mucocutaneous Involvement
 Psoriatic skin lesions
 Psoriatic Nail lesions
 Entheseal Involvement
 Ten...
Dactylitis
Nail changes
Occur in 90% of patients with PsA
 Pitting
 Horizontal ridging
 Onycholysis
 Yellowish discoloration of t...
Psoriasis/Nail changes/arthritis DIPs
and Sausage deformity
Classification of Psoriatic
Arthritis (CASPAR) criteria; 2006
A patient must have inflammatory articular disease (joint,
s...
Physical Examination
 Skin and Nail Involvement
 Peripheral Joint Involvement
 Peripheral Entheseal Involvement
 Spina...
 assessment of less
conspicuous areas
including
 gluteal cleft
 scalp
 scalp line
 groin
 posterior
auricular region...
Peripheral Joint Involvement
 Inflammatory Joint Count
 Number of Joints Involved
○ Prognostic Importance
○ Therapeutic ...
Laboratory investigations
 ESR and CRP elevated
 Uric acid may be elevated in the
presence of extensive psoriasis
 HLA-...
Radiographic features
Small joints involvement
 classic "pencil-in-cup" deformity
 marginal erosions
 adjacent bony pro...
Fusion
Pencil in Cup
deformity
•Subchondral bone resorption of
the distal interphalangeal joint of
the thumb and middle fi...
Radiology
Axial involvement
 Asymmetric sacroiliitis
 Syndesmophytes
 Fluffy hyperperiostosis on anterior vertebral bodies
 Seve...
Prognosis
 Erosive disease develops in the majority
 Progressive disease with deformity and disability
is common
 Morta...
Indicators of Bad
Prognosis
 Younger age at onset
 Presence of certain HLA antigens:
o HLA-B27 correlates with spondylit...
Differntial diagnosis
 Gout
 Inflammatory Osteoarthritis
 Multicentric reticulohistiocutosis
 Other forms of SpA
How to Tell the Difference
Treatment
 coordinated therapy is directed at both the skin and
joints
 anti-TNFagents - revolution
• Etanercept
• Infli...
 A relationship between arthritis and IBD
 Ulcerative colitis (UC) as well as
Crohn's disease (CD)
 prevalence of IBD i...
 tendency to familial aggregation, more so for
CD
 HLA-B27 - 70% of patients with IBD and AS
-15% of patients with IBD a...
Pathology
Similar to other spondyloarthritides
1. Enthesiopathy (7%)
2. Spondylitis (2%)
3. Peripheral arthritis (10%)
Pathogenesis
 The specific pathogenic mechanisms are
poorly understood
 Immune-mediated
 Trafficking of leukocytes betw...
Clinical Features
 AS - clinically indistinguishable from idiopathic AS
course independent of the bowel disease
 periphe...
Extraintestinal
manifestations
Uveitis
Pyoderma gangrenosum
Erythema nodosum
Finger clubbing
In IBD-associated SpA, erythema nodosum can be
observed in Crohn's disease
Laboratory Findings
 inflammatory and metabolic
manifestations of IBD
 Joint fluid is usually at least mildly
inflammato...
Radiographic
Findings
 axial skeleton are the same as in
uncomplicated AS.
 Erosions are uncommon in peripheral
arthriti...
Differential diagnosis
(Diarrhea and arthritis)
Reactive arthritis
Celiac disease
Blind loop syndromes
Whipple's disea...
Treatment
anti-TNF agents
• Infliximab
• adalimumab
Other treatment for IBD
 sulfasalazine and related drugs,
 systemic ...
 Approximately one-half of the patients with
undifferentiated SpA are HLA-B27-positive
 often eventual progression to cl...
 In juvenile-onset SpA - begins between ages 7 and 16
o most commonly in boys (60–80%)
o an asymmetric, predominantly low...
management
 anti-TNF- therapy
 Newer - doxycycline and rifampin
SYNOVITIS
ACNE -CONGLOBATA,
FULMINANS,
HIDRAENITIS SUPURATIVA
PUSTULOSIS -PALMO PLANTAR
HYPEROSTOSIS - STERNO-CLAVICULAR
S...
 In some cases, bacteria, most often
Propionibacterium acnes, have been cultured
 ESR is usually elevated, sometimes
dra...
Management
 High-dose NSAIDs
 Pamidronate or other
bisphosphonates
 Anti-TNF therapy
 Rare chronic bacterial infection, mostly
of middle-aged white men, caused by
Tropheryma whipplei
 75% of affected indiv...
 systemic disease
 PCR amplification
 penicillin (or ceftriaxone) and Streptomycin for
2 weeks
followed by
 trimethopr...
SPONDYLOARTHOPATHIES
A summary
 Absence of rheumatoid factor
 Involvement of sacroiliac and spinal joints
 Peripheral a...
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Spondyloarthropaties

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All about Spondyloarthropaties also known as Seronegative Arthritis in a nutshell....includes Pathology,signs and symptoms, investigations, and latest approved treatment of all subtypes....compiled from Turek and Harrisons textbook.

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Transcript of "Spondyloarthropaties"

  1. 1. (Seronegative arthritis) DR. PRUTHVIRAJ NISTANE Post-Graduate student Deptt. Of Orthopaedics, Govt. Medical College and Rajindra Hospital, Patiala
  2. 2. Objectives  Gain a basic understanding of the Spondylo- Arthritis  Learn specific Characteristics of SpA  Differentiate SpA from other chronic Arthritis ( RA, OA )  Become familiar with articular and extra-articular manifestations of SpA  Understand the current treatment paradigm and medications used
  3. 3. Introduction  Are a diverse group of chronic, systemic inflammatory conditions linked by distinctive clinical, radiographic, and genetic features  Refers to inflammatory changes involving the spine and the spinal joints.  subtypes often overlap  may be considered one heterogeneous and phenotypically diverse disease that has the potential to evolve into AS.
  4. 4. Introduction  Absence of Rheumatoid Factor or other autoantibody serologic abnormalities  includes ○Ankylosing Spondylitis ○Psoriatic Arthritis ○Reactive Arthritis ○Enteropathic Arthritis-IBD ○Undifferentiated Spondyloarthropathy
  5. 5. ESSG (Europian SpA Study Group)Criteria for diagnosis of spondyloarthropathy  Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs) plus more than 1 of the following:  Positive family history  Psoriasis  Inflammatory bowel disease  Urethritis, cervicitis, or acute diarrhea < 1 mo. before arthritis  Buttock pain alternating between right and left gluteal areas  Enthesities  Sacroiliitis  Sensitivity 78.4% and specificity 89.6%
  6. 6. RA SpA • UE>LE • Often polyarticular • Sacroiliitis absent • RF usually pos • No HLA-B27 assoc • Sicca, scleritis • LE>UE • Oligoarticular • Sacroiliitis often + • RF neg • + HLA-B27 assoc • Anterior uveitis • Mucocutaneous
  7. 7. Confusion Can often see peripheral joint symptoms in the absence of spinal symptoms
  8. 8. Pathology  immune  The pathology of spondyloarthropathies is very different from that of RA. In RA, it is the synovitis that plays the major role, and the synovitis leads to bony erosions.  In spondyloarthritis there is some synovitis, but it's the enthesitis that is the major problem, especially in the axial disease.
  9. 9. Pathology Osteitis follows reactive bone sclerosis and bone absorption, but then more bone remodeling sets in and it goes on to result in new bone formation that can result in ankylosis
  10. 10. Pathology  In RA, the cytokines lead to excessive osteoclastic activity resulting in bone erosions,  In spondyloarthritis, the cytokines that are playing a major role result in osteoblastic activity  Gradual bony bridging follows after being initiated by the inflammation
  11. 11. Hallmarks Inflammatory back pain (IBP) Enthesitis - inflammation at sites where tendons, ligaments, and joint capsule fibers attach to bone, with a strong tendency to produce fibrosis and calcifications.
  12. 12. Inflammatory Back Pain  Worse in the late night and early morning  Pain interferes with sleep to the point that the patient gets up to walk in the middle of the night  The discomfort can be characterized by alternating buttock pain.  prolonged morning stiffness of greater than 30 minutes.
  13. 13. Inflammatory Back Pain  Exercise alleviates the pain rest makes it worse.  Affects younger patients  Peaking during the mid-20s  onset before the age of 40
  14. 14. Spondyloarthropathies IBP persists for at least 3 months. detrimental effects on quality of life  increased disability, and morbidity -- equal, and in some cases exceeding, that seen in RA
  15. 15. Spondyloarthropathies  Also associated with osteoporosis and low bone mineral density  Ectopic bone formation occurs within the inflamed vertebral enthesis  Bone resorption, (increased osteoclast activity), occurs at an unregulated rate within the vertebra and promotes weakening of the spinal column.
  16. 16. Clinical course  The spine in the patient with AS fuses through:  ligamentous ossification and  syndesmophytosis,  Rigid hyperkyphotic deformity develops.  Biomechanically, the fused spine acts as a long bone incapable of appropriately dissipating the energy of a traumatic event.
  17. 17. Spondyloarthropathies  Altered spinal biomechanics  Combined with the brittle quality of the osteoporotic bone  Increase susceptibility to vertebral column factures, and Spinal Cord injury, even after minor, often trivial, trauma  Significantly impaired mobility and peripheral joint arthritis
  18. 18. Sagittal reformatted CT scan showing a highly displaced thoracic fracture. Asterisk indicates apposition of the caudal fracture fragment on the thoracic aorta
  19. 19. Extra-articular manifestations  psoriasis,  anterior uveitis,  IBD,  as well as rarer cardiac, renal, and pulmonary manifestations  a wide range of clinical manifestations.
  20. 20. Ocular Manifestations  Uveitis is one of the most common  occurring in 25% to 40% of patients.  there appears to be no correlation between the course of inflammatory eye disease and that of the arthritis.
  21. 21. Ocular Manifestations  Presents as acute unilateral pain and photophobia  Blurring of vision may also occur.  Cataracts  Glaucoma  Increased intraocular pressure  Posterior synechiae  Conjuctivities
  22. 22. Cutaneous Manifestations  Plaque psoriasis  Characterized by scaly, erythematous, hyperkeratotic lesions  most common form of psoriasis and is an important component of diagnosing PsA.
  23. 23. Cutaneous Manifestations  assessment of less conspicuous areas including  gluteal cleft  scalp  scalp line  groin  posterior auricular regions should be performed.
  24. 24. Nail Changes  Diffuse and numerous nail pitting (plate depressions)  Onicholysis (separation of the nail from underlying nail bed)  Crumbling of the nail plate can be observed in both psoriasis and PsA.  The extent of nail involvement parallels both skin and joint disease
  25. 25. Nail Pitting
  26. 26. Onicholysis toe nails
  27. 27. Crumbling nail/DIP joint involvement
  28. 28. Other Extra- articular Manifestations  Apical pulmonary fibrosis : mostly asymptomatic and typically observed in patients with substantial disease duration  Renal disease : beyond analgesic and nonsteroidal anti-inflammatory drug adverse effects  IgA nephropathy : proteinuria and hematuria  secondary amyloidosis : nephrotic syndrome  renal failure : a poor prognosis.
  29. 29. Gene association  Up to 70% of individuals suffering from SpA carry the HLA-B27 gene  Strength of the association between HLA- B27 and disease susceptibility varies among SpA subtypes and ethnic groups
  30. 30. Associations with HLA-B27 Rheumatic diseases Ankylosing spondylitis Reiter’s syndrome/reactive arthritis IBD related arthritis Psoriatic arthritis Normal Associations Native Americans Caucasians Blacks Degree of associations >90% >80% ~75% ~50% 13% 8% 4%
  31. 31. (MARIE-STRUMPELL DISEASE) (BECHTEREW DISEASE)
  32. 32.  A chronic, progressively inflammatory disease of the spine and axial joints leading to fibrous or bony ankylosis and deformity.  Systemic disease  Age – late adolescence or early childhood (20-40 yrs)  Sex - 3:1 men: women  Affects about 6 in 10,000
  33. 33. Etiology  Not completely understood  Auto-immune  HLA-B27 : seen in 90 % patients  Autosomal inheritance with 70 % penetration in males  some family history
  34. 34. Pathology  Most striking feature - high degree of fibrosis, bony ankylosis, and inflammation that focus on bone, cartilage, and tendon-bone junction.  Early lesions include subchondral granulation tissue that erodes the joint and is replaced gradually by FIBROCARTILAGE and then OSSIFICATION.  Occurs in ligaments, fibrocartilage,disc and capsular attachment sites to bone,called “enthesitis” )
  35. 35. Gross Pathology  Start from SI joint  Destruction of cartilage and articular cortex  Fibrous or bony bridging  Para-articular – degeneration and ossification in spine ossification of anterior longitudinal ligaments “bamboo spine”
  36. 36. HistoPathology Inflammatory cells in ligamentous and periosteal area Subchondral marrow oedema Pannus and new bone formation Bony erosion Fibrocartilagenous regeneration and ossification
  37. 37. Clinical features  Insidious onset  Begins in the Sacroiliac Joints –  backache and morning stiffness  radiation  U/L or B/L  subsides with activity  returns after sitting in one position for long period  Flexor spasm predominateforward flexion  Progresses upwards and can involve the entire spine
  38. 38. Axial joints(a poor prognostic )  Shoulders  Hips  Knees Painful,swollon, effusion, muscle spasms Flexion, adduction deformities
  39. 39. Peripheral joints  Osteoporosis  Blurring of margins  Joint space narrowing  Bony ankylosis • Kyphosis • Loss of spinal mobility • Decreased chest expansion
  40. 40. Systemic features  Fatigue  Weight loss  Anorexia  Night sweats  Anemia
  41. 41. Diagnosis Modified New York criteria (1984) 1. Limited lumbar motion 2. Low back pain for 3 months improved with exercise not relieved by rest with morning stiffness 3. Reduced chest expansion 4. Definite radiological sacroilitis Criteria 4 plus any of 1, 2, or 3.
  42. 42. Juvenile Ankylosing Spondylitis Onset 8 to 14 Sex Ratio M:F 7 to 1 HLA-B27 91 % Systemic symptoms rare Polyarticular 97% Prognosis good  Peripheral joint involvement is more to begin with; later axial symptoms supervene
  43. 43. Physical Examination  Loss of spinal mobility  Para spinal spasm
  44. 44. Spinal Involvement  Tenderness – SI joints  SI Compression Testing  Modified Schober Test  Potentially useful diagnostically  Limitation of motion
  45. 45. •Occiput to Wall distance •Chest Expansion  at the xiphisternum  Normally > 5 cm  Measurement is age and sex dependant  Useful for following patients over time
  46. 46. Spinal Involvement  Finger Tip to Floor Distance  Measure fingertips to floor  Useful for following patients over time Lateral Flexion  Ask the patient to flex laterally and mark at the maximal extent of the fingertips  Useful for following patients over time  Cervical Spine  Can result in Atlanto-Axial Instability
  47. 47. Radiological features  Within 3 to 6 months  SI joints – earliest  Patchy osteoporosis  Margins ill defined  Widened  Later subchondral sclerosis  Finally bridging and obliteration of joint
  48. 48. Sacroiliitis grading 0-normal 1-possible 2-minimal 3-moderate 4-ankylosing
  49. 49. The Spine  Sharp squaring of anterior portion of vertebral body  Loss of concavity  Loss of lardosis  Subluxation of atlanto-axial joint destruction of transverse ligament and odontoid
  50. 50. •The reparative process forms vertical linear bone ossification along the outer fibers of the annulus fibrosus of the disc, called syndesmophyte formation. •Ossification of anterior longitudinal ligament and annulus – “bamboo spine” •Vertebral bodies tend to become osteoporotic (dorsal spine appears to become wedge-shaped)
  51. 51. MRI – Early changes
  52. 52. Progression and complications Early stage(inflammatory)  Intermittent, low-grade fever  Fatigue  Anorexia  Sacroilitis (inflammation, pain, and tenderness in the sacroiliac joint)  Spasm of the vertebral muscles  Intermittent, low back pain (non-traumatic, insidious onset)  Rarely remission within 2 years
  53. 53. Advanced stage(ankylosis)  Constant low back pain  Ankylosis , decreased ROM  Muscle wasting in shoulder and pelvic girdle  Loss of lumbar lordosis  Marked dorsocervical kyphosis  Ultimately in 3 to 5 years – SI joints are fused, spine , hips ankylosed in forward flexion, single rounded immobile spinal curve , residual motion in knees and shoulder.
  54. 54. Complications  Fractures - Stiff osteoporotic spine is prone to fracture and minor trauma. Most common site of fracture is the lower cervical spine.  Progressive myelopathy - develops from cord compression leading to motor/sensory disturbance.  Cauda equina syndrome – late complication Initial deficit is loss of sensation on the lower extremity
  55. 55.  Spinal stenosis – rare ; Result of bony overgrowth of the spinal ligament and facet joint.Symptoms are pain and numbness of the lower extremities brought on by walking and relieved by rest.  Subluxation of atlanto-axial joint - chin-on-chest deformity  Reduced vital capacity
  56. 56. Associated symptoms  Aortitis  Aortic dilatation  Aortic regurgitation – scar tissue in aortic valves  Conduction abnormalities  Apical pulmonary fibrobullous lesion  Iritis  Non-granulomatous anterior uveitis  Colitis
  57. 57. Laboratory Investigations • Elevated ESR/CRP  HLA-B27 - found in 90-95% of patients ( 6% of general population) • Synovial fluid – mononuclear leukocytes  CBC  Normochromic normocytic anemia  Reactive thrombocytosis • Elevated serum IgA • Increased ALP • Decreased vital capacity
  58. 58. Differential diagnosis  Ankylosing form of RA  Other spondyloarthropathies  Other causes of LBA  Ochronosis  DISH
  59. 59. Treatment - Goals  Rehabilitation.  Initiated before the disease fuses the vertebrae and involves other organ.  Directed toward maintaining function and strength.
  60. 60. Conservative management  Corticosteroids – reduces inflammation and relieves pain may overcome deformity to some extent  NSAIDS - mainstay of treatment  Radiation – relieves muscle spasm given with caution  Methotrexate  Sulfasalazine
  61. 61. Latest revolution  Anti TNF-α therapy Infliximab Etanercept  Rapid, profound and sustained response to all aspects of disease  Serious complications  Very expensive
  62. 62. Posture and exercise  Recumbence  Hyperextension , abduction  Deep breathing exercises  Traction to lower extremities to overcome deformity
  63. 63. Surgical management  To relieve from disabling deformities Total hip replacement  Neck osteotomy and head removed piecemeal  Accurately identify acetabular margins  Over come flexion, stooping  Motion  Relieve pain  Restore upright posture  Prevent spinal osteotomy  90 % good results
  64. 64. Spinal osteotomy Done at L2-3 or L3-4 level Wedge of posterior spinal column excised and straightening of spine done. Multiple complications
  65. 65. Thank you
  66. 66. (Seronegative arthritis) II Moderated by - Dr. K. S. Sandhu Presented by - Dr. Pruthviraj Nistane
  67. 67. “Recap”  Are a diverse group of chronic, systemic inflammatory conditions linked by distinctive clinical, radiographic, and genetic features  Refers to inflammatory changes involving the spine and the spinal joints.  subtypes often overlap
  68. 68. ESSG (Europian SpA Study Group)Criteria for diagnosis of spondyloarthropathy  Inflammatory spinal pain or synovitis (asymmetric or predominantly in lower limbs) plus more than 1 of the following:  Positive family history  Psoriasis  Inflammatory bowel disease  Urethritis, cervicitis, or acute diarrhea < 1 mo. before arthritis  Buttock pain alternating between right and left gluteal areas  Enthesities  Sacroiliitis  Sensitivity 78.4% and specificity 89.6%
  69. 69. Hallmarks  Immune mediated enthesitis and other changes  IBP  Extra-skeletal manifestations  Association with HLA – B27
  70. 70. ANKYLOSING SPONDYLITIS  PROTOTYPE  Most common  Crippling disease affecting young population  Inflammatory back pain  From sacro-ilitis to complete fusion on the spine  Large peripheral joints may be involved  Anti TNF agents have revolutionised treatment
  71. 71. (Reiter’s syndrome)
  72. 72. What is it ???  Acute non-purulent arthritis complicating an infection elsewhere in body  Clinical syndrome triggered by specific etiological agent in genetically susceptible host  Infection – mostly enteric or urogenital
  73. 73. “Reactive”  viable micro-organisms do not enter the joints and synovial fluid cultures are thus negative.  There is no universal agreement about the classification and diagnostic criteria for reactive arthritis.
  74. 74.  Reiter’s syndrome –old aponym for reactive arthritis  clinical triad of arthritis, urethritis and conjunctivitis.  Reactive arthritis belongs to the family of spondyloarthropathies because they share cardinal clinical features together.
  75. 75. Epidemiology  age - is 18–40 years  gender ratio in ReA following enteric infection is nearly 1:1, whereas venereally acquired ReA occurs mainly in men  60–85% of patients were found to be B27- positive - its presence contributes to the chronicity of the disease.
  76. 76. Triggering infections • Reactive arthritis is an arthritis induced by one of the following bacteria:  Urogenital: • Chlamydia trachomatis  Enteric: • Shigella (S. flexneri has most often) • Salmonella • Yersinia • Campylobacter • At least presumptive evidence for a related antecedent infection is a must
  77. 77.  Form of post infection arthritis that share same clinical features as SpA.  Whereas arthritis caused by or related to other infections is termed “infection- related/ associated arthritis”
  78. 78. Pathology • Synovial histology - is similar to that of other SpA • Enthesitis - increased vascularity Macrophage infiltration of fibro cartilage • Histopathology evidence of inflammation has occasionally been noted in the colon and ileum
  79. 79. Pathogenesis Bacterias • produce lipopolysaccharide (LPS) • capacity to attack mucosal surfaces, • survive intracellularly HLA-B27 - prolongs the intracellular survival Trafficking of infected leukocytes from the site of primary infection to joints, where an innate and adaptive immune response to persistent bacterial antigens promote arthritis. synovial T cells that specifically responded to antigens of the inciting organism were reported and characterized as predominantly CD4+ with a TH2 or T regulatory phenotype. More recent work has documented high levels of IL-17
  80. 80. confusion ???? • Antigens from these bacterias have been shown to be present in the synovium and/or synovial fluid leukocytes • So atleast in some cases,it may be chronic form of infection rather than solely reactive
  81. 81. Clinical picture  Usually there is a delay of 1-4 wks from infection till start of arthritis  ranges from an isolated, transient monarthritis or enthesitis to severe multisystem disease  History suggestive of infection
  82. 82. Musculoskeletal symptoms Peripheral • Typically there is asymmetric additive, oligoarthritis, mainly of Lower limbs. • Most common are knees, ankles, subtalar , toe IP and MTP joints. • Quite painful, and tense joint effusions. • Dactylitis, or "sausage digit " a diffuse swelling of a solitary finger or toe, is a distinctive feature of peripheral SpA
  83. 83. Axial • Inflammatory low back pain o Acute sacroiliitis o insertional inflammation, o muscle spasm o arthritis in intervertebral joints. • Enthesitis • Plantar fasciitis • Achilles tendinitis
  84. 84. Extra-articular features in ReA Mucocutaneous • Keratoderma Blennorrhagica (20%) palms and soles • Circinate balantitis (30%) • Painless oral ulcers (25%) • Erythema nodosum Nail changes • onycholysis, • distal yellowish discoloration • heaped-up hyperkeratosis.
  85. 85. Pustules KB
  86. 86. Keratoderma Blenorrhagicum
  87. 87. Urogenital lesions males • urethritis • Prostatitis females • Cervicitis • salpingitis Ocular • Conjunctivitis (60%) • Uveitis (unilateral) (20%) • urethritis• Cervicitis
  88. 88. Constitutional symptoms  Fatigue  Malaise  Fever  Weight loss  Cardiac conduction defects  Aortic insufficiency  Central or peripheral nervous system lesions  Pleuropulmonary infiltrates.
  89. 89. Diagnostic Criteria • Seronegative asymmetric arthropathy and at least 1 of the following: • Urethritis or cervicitis • Diarrhea • Inflammatory eye disease • Mucocutaneous disease • Balanitis, oral ulceration or keratoderma • Other spondyloarthropathies and rheumatic disease excluded
  90. 90. Prognosis  Persists 3–5 months, but courses up to 1 year can occur.  Chronic joint symptoms persist in about 15% of patients.  Recurrences of the acute syndrome are also common  Low-back pain, sacroiliitis, and frank AS are also common sequelae
  91. 91. Laboratory investigations Demonsration of the urogenital tract or bowel infections  During the acute phase: • urine culture, • genital swabs, • stool culture  After arthritis developed: • Serodiagnosis to detect antibodies • PCR
  92. 92.  inflammatory arthritis: • ↑ESR, CRP • leucocytosis • Synovial fluid analysis and culture  HLA B27 (especially in chronic arthritis)-85 %  Imaging : MRI, CT, Plane x-ray for detection of • Sacroilitis – asymmetrical • Enthesopathy • Juxtaarticular osteoporosis • Marginal erosions • Loss of joint space • Spondylitis – can begin anywhere in lumbar spine • Reactive new bone formation Laboratory investigations
  93. 93. Differintial diagnosis  Disseminated gonococcal disease  psoriatic arthropathy  Other spondyloarthropathies
  94. 94. Treatment  Eradicate triggering infection (antibiotics)  Treat extra-articular manifestations: Topical steroid Uveitis - topical steroids, mydriatics  Skin lesions ordinarily require only symptomatic treatment
  95. 95. 1. NSAIDs: in full doses Indomethacin, 75–150 mg/d in divided doses is the initial treatment of choice 2. Local steroids injections in mono/oligo arthritis, enthesopathy 3.Immuno-suppresants • Sulfasalazine • Azathioprine • methotrexate 4. Biologics: anti-TNF- α in resistant disease Treatment of arthritis:
  96. 96. PSORIATIC ARTHRITIS
  97. 97. What is it ???  Psoriatic arthritis (PsA) refers to an inflammatory arthritis that characteristically occurs in individuals with psoriasis.
  98. 98. Who Gets Psoriatic Arthritis?  Age of onset - 30-50 years  1-3% of the population has psoriasis  5 – 10 % of people with psoriasis get psoriatic arthritis  Family studies suggest a 50-fold increase in the risk of psoriatic arthritis in 1st degree relatives  HLA-Cw6 gene is directly associated with psoriasis  HLA-B27 is associated with psoriatic spondylitis
  99. 99. Pathology  shares pathogenic mechanisms with psoriasis  immune-mediated  Infiltration with T cells, B cells, macrophages, and NK receptor–expressing cells  Resembles that of RA - less hyperplasia and cellularity than in RA, & greater vascularity
  100. 100. Pathology  synovial overexpression of proinflammatory cytokines • Interleukin 2 • Interferon • TNF  marked increase in osteoclastic precursors in peripheral blood and upregulation of receptor activator of nuclear factor ligand (RANKL) in the synovial lining layer.
  101. 101. Clinical Features  Psoriasis present before the onset of joint disease (70%)  Psoriasis comes with the arthritis (15%)  Psoriasis comes after the arthritis (15%)
  102. 102. Confusion Psoriatic Arthritis is a heterogenous disease which can present in a multitude of ways
  103. 103. Wright and Moll Classification (1) Arthritis of the DIP joints; 15 % (2) Asymmetric oligoarthritis; 30 % (3) Symmetric polyarthritis similar to RA; 40 % (4) Axial involvement (spine and sacroiliac joints);5% (5) Arthritis mutilans, a highly destructive form of disease5 %
  104. 104. Arthritis of the DIP joints
  105. 105. Arthritis of the DIP joints
  106. 106. Asymmetric oligoarthritis
  107. 107. Asymmetric oligoarthritis
  108. 108. Symmetric polyarthritis
  109. 109. Axial involvement
  110. 110. Arthritis Mutilans
  111. 111. Arthritis Mutilans
  112. 112. Presentation  Typical presentation is a peripheral inflammatory joint disease – usually a mono or oligo arthritis  Knees  Wrists  May occasionally present with polyarthritis  Initial presentation of inflammatory spinal disease is rare
  113. 113. Progression -- later stages  Sacroiliac Involvement  Sacroiliitis in 1/3 of patients  Usually asymmetric (unilateral)  May be asymptomatic  Spinal Involvement  May affect any part of the spine in a random fashion  Different from ankylosing spondylitis
  114. 114. Other features  Mucocutaneous Involvement  Psoriatic skin lesions  Psoriatic Nail lesions  Entheseal Involvement  Tenosynovities  Dactylitis ->30 % • Shortening of digits because of underlying osteolysis • Both fibrous and bony ankylosis of small joints • Ankylosis of one or more PIP joint  Ocular Involvement - uveitis - bilateral, chronic, and/or posterior, - conjuctivitis  Aortic valve insufficiency
  115. 115. Dactylitis
  116. 116. Nail changes Occur in 90% of patients with PsA  Pitting  Horizontal ridging  Onycholysis  Yellowish discoloration of the nail margins  Dystrophic hyperkeratosis  Combinations
  117. 117. Psoriasis/Nail changes/arthritis DIPs and Sausage deformity
  118. 118. Classification of Psoriatic Arthritis (CASPAR) criteria; 2006 A patient must have inflammatory articular disease (joint, spine, or entheseal) with 3 points from any of the following five categories: 1) Evidence of current psoriasis,or history of it 2) Typical psoriatic nail dystrophy 3) A negative test result for rheumatoid factor 4) Either current dactylitisf or a history of it 5) Radiographic evidence of juxtaarticular new bone formation in the hand or foot
  119. 119. Physical Examination  Skin and Nail Involvement  Peripheral Joint Involvement  Peripheral Entheseal Involvement  Spinal Involvement  Schober Test  Occiput to Wall Distance  Spine ROM  Finger tip to floor distance  Lateral flexion
  120. 120.  assessment of less conspicuous areas including  gluteal cleft  scalp  scalp line  groin  posterior auricular regions should be performed.
  121. 121. Peripheral Joint Involvement  Inflammatory Joint Count  Number of Joints Involved ○ Prognostic Importance ○ Therapeutic Importance  Pattern of Joints Involved ○ Diagnostic Importance  Evidence of Damage  Dactylitis
  122. 122. Laboratory investigations  ESR and CRP elevated  Uric acid may be elevated in the presence of extensive psoriasis  HLA-B27 is found in 50–70% of patients with axial disease, but 20% in patients with only peripheral joint involvement.
  123. 123. Radiographic features Small joints involvement  classic "pencil-in-cup" deformity  marginal erosions  adjacent bony proliferation(whiskering)  small-joint ankylosis  osteolysis of phalangeal and metacarpal bone  telescoping of digits  Periostitis  proliferative new bone at sites of enthesitis.
  124. 124. Fusion Pencil in Cup deformity •Subchondral bone resorption of the distal interphalangeal joint of the thumb and middle fingers has resulted in the "pencil-in- cup" appearance. •A flexion deformity of the distal interphalangeal joint of the small finger is present •corresponding joint of the ring finger has fused.
  125. 125. Radiology
  126. 126. Axial involvement  Asymmetric sacroiliitis  Syndesmophytes  Fluffy hyperperiostosis on anterior vertebral bodies  Severe cervical spine involvement, with a tendency to atlantoaxial subluxation  Sparing of the thoracolumbar spine  paravertebral ossification
  127. 127. Prognosis  Erosive disease develops in the majority  Progressive disease with deformity and disability is common  Mortality was found to be significantly increased compared with the general population  The psoriasis and associated arthropathy seen with HIV infection both tend to be severe and can occur in populations with very little psoriasis
  128. 128. Indicators of Bad Prognosis  Younger age at onset  Presence of certain HLA antigens: o HLA-B27 correlates with spondylitic involvement o HLA-DR3, DR4 correlates with erosive disease  Extensive skin involvement  Polyarticular involvement  Lack of clinical response to NSAIDs  Association with HIV infection
  129. 129. Differntial diagnosis  Gout  Inflammatory Osteoarthritis  Multicentric reticulohistiocutosis  Other forms of SpA
  130. 130. How to Tell the Difference
  131. 131. Treatment  coordinated therapy is directed at both the skin and joints  anti-TNFagents - revolution • Etanercept • Infliximab • Adalimumab • Golimumab.  Methotrexate  Sulfasalazine  leflunomide  PUVA  7 % of patients with PsA required musculoskeletal surgery
  132. 132.  A relationship between arthritis and IBD  Ulcerative colitis (UC) as well as Crohn's disease (CD)  prevalence of IBD is 0.05–0.1%,  AS was diagnosed in 1–10%, and peripheral arthritis in 10–50% of patients with IBD  one-third to two-thirds of patients with AS have subclinical intestinal inflammation
  133. 133.  tendency to familial aggregation, more so for CD  HLA-B27 - 70% of patients with IBD and AS -15% of patients with IBD and peripheral arthritis  alleles of the NOD2/CARD15 gene in SpA patients with chronic inflammatory gut lesions
  134. 134. Pathology Similar to other spondyloarthritides 1. Enthesiopathy (7%) 2. Spondylitis (2%) 3. Peripheral arthritis (10%)
  135. 135. Pathogenesis  The specific pathogenic mechanisms are poorly understood  Immune-mediated  Trafficking of leukocytes between the gut and the joint  Mucosal leukocytes from IBD patients have been shown to bind avidly to synovial vasculature
  136. 136. Clinical Features  AS - clinically indistinguishable from idiopathic AS course independent of the bowel disease  peripheral arthritis - includes acute self-limited attacks of oligoarthritis (4-6 weeks) of LL chronic and symmetric polyarticular arthritis course parallel to disease  Enthesitis , arthralgias or fibromyalgia symptoms.
  137. 137. Extraintestinal manifestations Uveitis Pyoderma gangrenosum Erythema nodosum Finger clubbing
  138. 138. In IBD-associated SpA, erythema nodosum can be observed in Crohn's disease
  139. 139. Laboratory Findings  inflammatory and metabolic manifestations of IBD  Joint fluid is usually at least mildly inflammatory  30–70% carry the HLA-B27 gene,
  140. 140. Radiographic Findings  axial skeleton are the same as in uncomplicated AS.  Erosions are uncommon in peripheral arthritis but may occur, particularly in the metatarsophalangeal joints.  Isolated destructive hip disease has been described.
  141. 141. Differential diagnosis (Diarrhea and arthritis) Reactive arthritis Celiac disease Blind loop syndromes Whipple's disease
  142. 142. Treatment anti-TNF agents • Infliximab • adalimumab Other treatment for IBD  sulfasalazine and related drugs,  systemic glucocorticoids  immunosuppressive drugs usually of benefit for associated peripheral arthritis.
  143. 143.  Approximately one-half of the patients with undifferentiated SpA are HLA-B27-positive  often eventual progression to classical AS
  144. 144.  In juvenile-onset SpA - begins between ages 7 and 16 o most commonly in boys (60–80%) o an asymmetric, predominantly lower-extremity oligoarthritis and enthesitis without extraarticular Features  The prevalence of B27 in this condition, which has been termed the seronegative enthesopathy and arthropathy (SEA) syndrome, is approximately 80%.
  145. 145. management  anti-TNF- therapy  Newer - doxycycline and rifampin
  146. 146. SYNOVITIS ACNE -CONGLOBATA, FULMINANS, HIDRAENITIS SUPURATIVA PUSTULOSIS -PALMO PLANTAR HYPEROSTOSIS - STERNO-CLAVICULAR SPINAL OSTEOMIELITIS - STERIL MULTIFOCAL RECURRENT
  147. 147.  In some cases, bacteria, most often Propionibacterium acnes, have been cultured  ESR is usually elevated, sometimes dramatically  Inflammatory bowel disease was coexistent in 8%  B27 is not associated
  148. 148. Management  High-dose NSAIDs  Pamidronate or other bisphosphonates  Anti-TNF therapy
  149. 149.  Rare chronic bacterial infection, mostly of middle-aged white men, caused by Tropheryma whipplei  75% of affected individuals develop an oligo- or polyarthritis.  Joint manifestations usually precede other symptoms of the disease by 5 years or more  Large and small peripheral joints and sacroiliac joints may be involved.  abrupt in onset, migratory, usually lasts hours to a few days
  150. 150.  systemic disease  PCR amplification  penicillin (or ceftriaxone) and Streptomycin for 2 weeks followed by  trimethoprim-sulfamethoxazole for 1–2 years
  151. 151. SPONDYLOARTHOPATHIES A summary  Absence of rheumatoid factor  Involvement of sacroiliac and spinal joints  Peripheral arthritis (predominantly lower limb)  Enthesopathy  Familial clustering  Increased incidence of HLA-B27  Common spectrum of extra-articular features (predominantly muco-cultaneous)  Anti TNF agents are the latest revolution !
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