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Chapter: Medicine Study Notes : Musculo-Skeletal

Spondyloarthropathies (Seronegative Arthritis)

Rheumatoid factor is negative – but exclude seronegative RA

Spondyloarthropathies (Seronegative Arthritis)


·        Rheumatoid factor is negative – but exclude seronegative RA

·        Clinical overlap between the conditions

·        Acronym: PEAR:  Psoriasis, Enteropathic, Ankylosing Spondolytis, Reactive/Reiter‟s

·        Have in common:

o   Involvement of spine and sacroiliac joints (= axial arthritis)

o   Usually asymmetrical large joint mono or oligo-arthritis

o   Inflammation then calcification of tendon insertions (enthesopathy)

o   Extra-articular manifestations: uveitis, aortic regurgitation, upper zone pulmonary fibrosis

o   Familial tendency + HLA-B27 +ive predisposition

·        If type not clear then classified as „Undifferentiated spondyl-arthropathy‟:


Ankylosing Spondylitis


·        = Chronic systemic inflammatory disorder of the axial skeleton, affecting SI joints and spine

·        Ankylosing = fibrous replacement of the joint ® bony fusion

·        Epidemiology:

o   Prevalence: 2 – 5 per 1,000 males.  Men have more progressive disease

o   Men more common and present earlier (6:1 at 16 years, 2:1 at 30 years)

o   Onset usually between 15 – 40 years

o   Closely linked to HLA-B27:

§  5 – 20% risk for positive individual

§  11 HLA subtypes identified with different disease susceptibilities 

§  Strong ethnic variances in HLA prevalence: present in Caucasians, absent in indigenous people of South America and Australia, high prevalence in Eskimos….

·        Clinical presentation:

o   75% first present with insidious onset of dull back ache, worse at night, improved by exercise 

o   Morning stiffness, backache, sacroiliac pain, loss of spinal movement (spinal ankylosis, distraction of < 10 cm on flexion with Schober‟s test)

o   Leading to flattening of lumber spine, thoracic kyphosis, neck hyperextension

o   Fatigue common

·        Distribution:

o   Sacroiliac joints and spine (lumbar to start with, C-spine later):

§  Bilateral sacro-iliac joint tenderness 

§  Tenderness of the lumbar vertebrae

§  Loss of thoracic kyphosis and lumbar lordosis 

§  Early restriction in lateral flexion of the spine – test by seeing how far they can slide their hand down the side of their leg without bending forward. Later loss of movement in all directions 

o  Hips (30%), also knees and shoulders

o  Peripheral arthritis infrequent

·        Other features:

o  Commonly:

§  Enthesitis

§  Iritis/Anterior Uveitis (25 – 30%): unilateral, acute, painful, with photophobia and blurred

§  vision.  To test: shining light in opposite eye causes pain in the affected eye

§  Costocondriasis + chest pain referred from thoracic vertebrae 

§  Chest wall rigidity ® ¯VC

§  Plantar fasciitis

o  Rare: 

§  Neurological involvement: secondary to spinal fracture (eg C-spine), atlanto-axial subluxation, cauda equina syndrome 

§  Amyloidosis 

§  Carditis and aortic regurgitation due to fibrosis of the aortic valve (can also affect AV bundle ® arrhythmias)

§  Apical lung fibrosis (rare)

·        Pathogenesis:

o  Cross reactivity between Klebsiella pneumoniae antigens and HLA B27 

o  Antibody complexes cause synovitis, enthesopathy (including tendon attachment calcification) ® capsular ossification, ankylosis (bony fusion) of the sacroiliac joint, inflammatory arthritis of the synovial joints in the spin and ossification of spinal ligaments


·        Diagnosis is clinical: History of inflammatory spine disease + SI tenderness, ¯L-spine mobility, ¯chest expansion


·        Differential from RA:

o  Spine rarely affect in RA

o  Small peripheral joints rarely affected in AS

o  In AS there are no subcutaneous nodules and no RF (but there may not be in RA either)

·        Investigations: 

o   X-rays: „bamboo‟ or „railroad‟ spine, squaring of vertebrae, syndesmophytes, erosions of the apophyseal joints (between rib tuberosities and spinal processes), eventually bony ankylosis of the

o   SI joints (also seen in Reiter‟s and Crohn‟s diseases)

o  Bloods:

§  FBC (mild normochromic anaemia in 15%) 

§  ­ESR and CRP

·        Treatment:

o  Physiotherapy/Exercise (not rest) to maintain posture and mobility

o  NSAIDs to relieve pain and stiffness (especially phenylbutazone).  If ineffective try sulphasalazine

o  Local corticosteroids for uveitis, enthesitis, peripheral synovitis

o  Disease Modifying drugs if severe


Psoriatic Arthritis


·        Epidemiology: occurs in 5 – 7% of psoriasis patients, age 35 – 45, male = female

·        Pathology:

o  Can have a reactive type presentation due to a host of possible infective/inflammatory agents 

o  Primary lesion = synovitis (similar to RA): hypertrophic villi, T-cell infiltration, aggregates of T cells. But usually only minimal joint impairment. Articular destruction in a subset (25%) with panus formation, cartilage erosion, etc = Arthritis Mutilans


·        Clinical presentation:

o  Usually psoriasis develops first, then arthritis, but 15% go the other way

o  Usually insidious but can present acutely

o  Check for nail pitting, transverse ridging, oncyholysis

o  Extra-articular manifestations are uncommon (except for conjunctivitis and iritis)


·        Distribution:

o   Often asymmetric, mainly oligo but can be poly arthritis

o   Often upper limb

o   DIP joints in hands and feet especially affected – unique to PA

o   Sacroiliac joints and spine (20 – 40%) – asymmetric involvement common

o   Rheumatoid pattern 

o   Inflammation of digital tendon sheaths ® sausage finger (dactylitis)

o   Enthesitis: Achilles tendonitis and plantar fasciitis


·        Diagnosis: Psoriasis (exclude seborrhoeic dermatitis and fungal infections) or psoriatic nail involvement + sero-negative arthritis. Increased likelihood in B27 +ive


·        Investigations: X-ray of hands ® DIP involvement + resorption of the terminal phalanges

·        Treatment:

o   NSAIDs for pain – but may worsen skin lesions

o   Corticosteroid injections for local synovitis

o   If severe: methotrexate, cyclosporin, sulphasalazine, gold etc

·        Differentiating from RA:

o   Presence of skin rash

o   Asymmetric

o   DIP and PIP involvement 

o   Can overlap with RA and present as a symmetrical, destructive arthritis. Look for psoriasis and nail changes


Reiter’s Syndrome


·        Classic triad: urethritis, conjunctivitis and seronegative arthritis. Recurrence in 50%, attacks can last several months

·        Caused by sterile synovitis following chlamydia/NSU/shigella infection

·        Distribution of arthritis usually lower limb (may be chronic or relapsing):

o   Sacroiliac joints and spine

o   Hips

o   Knees

o   Ankles and most of the joints of the feet

·        Other features:

o   Iritis

o   Keratoderma blenorrhagica (brown, aseptic abscesses on soles and palms)

o   Mouth ulcers

o   Circinate balanitis (painless serpiginous penile rash)

o   Enthesopathy (plantar fasciitis, Achilles tendonitis)

o   Not onycholysis (differentiates from psoriasis)

·        Investigations:


o   Chlamydia: First of 2 glass urine test shows more debris in the first glass in urethritis (cf prostatitis where there is more in the 2nd)

o   Anti-chlamydial antibodies

o   Neutrophils in synovial fluid

o   X-rays: periosteitis at ligamentous insertions.  Rheumatoid like changes if chronic


·        Pathogenesis: following non-specific urethritis, Chlamydia or Shigella infection in those genetically pre-disposed (ie HLA B27). Hyperaemic synovial membrane, but no panus or cartilage erosion (except if progressive). Profuse osteolysis and formation of new periosteal bone


·        Management: treat causal agent, rest, NSAIDs, steroid injections, recovery may be slow


Other Reactive Arthritis


·        Infective causes: Yersinia, Chlamydia, Campylobacter, Salmonella, Shigella, Clostridium difficile…

·        (all have lipopolysaccharide in their outer cell membrane) 

·        ® Sterile immunological reaction in joints due to cross reactivity of antigens

·        Usually B27+

·        Presentation: 

o   Acute asymmetrical polyarthritis (esp of lower limb) 1-2 weeks post infection lasting for 3 – 6 months

o   Can become chronic with relapsing and remitting course 

o   Enthesitis is common (eg ® plantar fasciitis or Achilles tendonitis)

o  Can also get: 

§  Skin lesions resembling psoriasis: Circinate balanitis, keratoderma blenorrhagica and nail dystrophy

§  Iritis

·        Investigations:

o  Causative agent: Blood culture/serology for antibodies/stool culture

o  HLA-B27, X-ray, ESR, joint aspiration for sceptic arthritis

·        Diagnosis is clinical

·        Management:

o  Treating persisting infection has little impact on course

o  NSAIDs/corticosteroids

o  Sulphasalazine etc if necessary 

·        Also in leukaemia, endocarditis, acne, acromegaly, Wilson‟s disease, sarcoid, sickle cell, haemochromatosis


Enteropathic Arthropathies


·        Associations:

o  Inflammatory bowel disease (15% of Crohn‟s and UC get arthritis)

o  Also associated with intestinal bypass surgery and Whipple‟s Disease

·        Asymmetrical lower large joint mono- or oligo arthropathy

·        No joint destruction

·        Sacroiliitis or Spondylitis in 5% (70% of these have HLA-B27)

·        Manage underlying condition:

o  Sulphasalazine for both bowel disease and arthritis

o  NSAIDs and steroid injections for monoarthritis


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