​rheumatology

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Osteoarthritis


Aust Prescr 2015;38:115-9
History
  • Quantifying the number of joints involved
  • The nature of the pain - trying to delineate the difference between inflammatory and non-inflammatory arthropathy (eg morning stiffness, gel phenomenon)
  • Effect on function
  • Risk factors - age, obesity, heritable, osteoporosis is protective, secondary osteoarthritis can occur secondary to trauma, bony deformities, inflammatory arthropathy
  • 50% radiological, 12% symptomatic. Implies radiology does not equate to symptoms
  • Disease of articular cartilage --> progressive loss
Examination
  • Bouchards/ heberdens, varus, joint tenderness, effusions, trendelemburgs, antalgic gait
Investigations
  • Clinical Dx supported by radiology
  • Normal inflammatory markers
  • Synovial fluid has high viscosity, cell count <2000
  • Imaging. X-ray (joint space narrowing, subchondral sclerosis, bony cysts, osteophytes), MRI after X-ray [bone marrow lesions = sclerotic but poorly mineralized bones, predict pain, cartilage damage and loss]
Management
  • Goals of Management:
    • short term - to acutely manage pain
    • medium and long term - improve functionality and mobility with improvements in quality of life
  • Non pharmacological
    •  Exercise is universally recommended by clinical guidelines, and should be individualised after patient assessment
    • ​​ Exercise has small to moderate effect sizes for improved function and pain relief, similar to those achieved with non-steroidal anti-inflammatory drugs (NSAIDs) and analgesia
    • If there are functional and mobility limitations then I would pursue water based exercise regimes
    • Targeted muscle exercises and aerobic exercises are generally recommended
    • Stretching and flexibility exercises generally form part of an overall exercise program for osteoarthritis, to maintain or increase the range of motion in the joints
    • Supervised exercises are better than individualised exercises with regards to pain reduction
    • Mobility aids such as a stick (used in the opposite hand), knee braces and foot orthoses can also diminish pain and improve function
    • Weight loss, as obesity is an important modifiable risk factor,  50% improvement in symptoms with 10% weight reduction through diet and exercise
  • Pharmacological
    • ​NSAIDS first line, efficacy is superior to paracetamol, combine with PPI if concerned - reduces dyspepsia by 66%
    • A meta-analysis of 26 studies comparing the two found that COX-2 inhibitors reduced the relative risk of dyspepsia by 12% and the absolute risk by 3.7%
    • Paracetamol no greater than placebo for knee arthritis, lower effect than NSAIDS, and safety concerns arising with regard to GI and multi-organ dysfunction
    • Topical NSAIDS - applied 3 - 4 times a day, works for knee and hand osteoarthritis, local drug delivery reduces GI side effects. An example is topical diclofenac sodium 1% gel. Topical capsaicin can also be used
    • Intra-articular injections - provide short-term pain relief (1–2 weeks in randomised controlled trials) and improved function for patients with osteoarthritis, intra-articular injections given more frequently than once every four months can result in cartilage and joint damage.
    • Opioids -  alternative for patients who cannot tolerate or be prescribed first-line drugs
    • ​Joint replacement surgery should be considered for severe clinical disease with inadequate response to conservative treatment.

Lumbar Spinal Canal Stenosis


BMJ 2016;352:h6234
General Information
  • degenerative condition in which changes in the discs, ligamentum flavum, and facet joints with aging cause narrowing of the spaces around the neurovascular structures of the spine
  • Most common indication for spinal surgery for age > 65
  • facet joint hypertrophy, loss of intervertebral disc height, disc bulging, osteophyte formation, and hypertrophy of the ligamentum flavum
  • extension of the lumbar spine reduces the size of the lumbar spinal canal, as does axial loading
History
  • Neurogenic claudication symptoms
  • progressive onset of pain, numbness, weakness, and tingling in the low back, buttocks, and legs, which is initiated by standing, walking, or lumbar extension
  • shopping cart sign - patient walking in a flexed or stooped position to relieve or reduce symptoms
  • DDx vascular claudication - exacerbation of symptoms with posture versus exertion
  • Most people with symptomatic LSS have limited walking capacity; they may require walking aids and may even avoid walking altogether
Examination
  • Balance impairment, neuromuscular deficits in the lower extremities including decreased strength (weakness), sensory deficits (numbness), and absent or decreased reflexes (Achilles tendon and patellar)
Investigations
  • MRI is best, gives good soft tissue detail, but review found it is similar to CT for the diagnosis of lumbar spinal canal stenosis
  •  anteroposterior diameter (<10 mm) and cross sectional area (<70 mm2) of the spinal canal
Management
  • Non-pharmacological
    • ​Physiotherapy related treatments include - balance training, specific exercise in lumbar flexion, lumber semi-rigid orthosis, braces and corsets
  • Pharmacological
    • Simple analgesia
    • NSAIDS equivalent to paracetamol
    • opioids may be used
    • low quality evidence for use of vitamin B1 and gabapentin
    • Injections
      • meta-analysis published in 2015 found that epidural steroid injections provide limited short term and long term improvement in pain and walking distance in patients with LSS
  • ​​Surgical
    • ​often an elective procedure 
    • decompression surgery for neurovascular structures
    • ​other procedures also exist, see review BMJ 2016;352:h6234

Crystal arthropathy


Crystals found in synovial fluid
  • Monosodium urate monohydrate = acute gout, tophaceous gout
  • Calcium pyrophosphate dehydrate = spectrum, acute pseudogout, destructive arthropathy, asymptomatic
  • Basic calcium phosphate = Milwaukee shoulder
  • Calcium oxalate = acute arthritis
  • Lipid = acute arthritis
Symptoms
  • Patients with an acute attack can often pinpoint the onset to the hour. They may describe the pain as the most severe they have ever experienced.
  • Morning stiffness is prominent and reflects the underlying inflammatory mechanism
  • Fevers, chills, malaise
  • Most commonly involved are joints in the feet, especially the first metatarsophalangeal, tarsometatarsal, and ankle joints
  • Pattern is usually monoarticular or oligoarticular (<4 joints). Can be polyarticular, affecting multiple joints in the hands and feet, especially in older people.
  • Presence of family members with gout at a fairly young age may suggest a genetic defect in a specific enzyme
  • Acute gout natural Hx favours self termination in majority, because blood and oedema increase pH, increase temp, decreases crystal formation; monoarticular mainly. This leads to an intercritical period for weeks/ months [ongoing damage can occur] --> complicated gout with longer duration, polyarticular in features and chronic tophaceous destructive gout [transitions to this when inter-critical periods no longer pain free
Pathophysiology (gout)
  • Increased production (10%)/ intake vs decreased clearance (90%)
  • Production: genetic due to PrPP synthetase mutation, acquired due to myeloprolif, high intake, alcohol, obesity, high trigs. 1/3 from diet, 2/3 endogenous
    • Urate produced from purines (dietary = red meat, seafood, bacon, dairy and coffee protective, alcohol = beer>wine>spirits, endogenous)
    • oestrogen reduces hyperuricaemia therefore less incidence in females cf males
    • transplant (tacro and cyclosporine are risk factors)
  • Reduced Excretion 90%: genetic due to HRPT mutation, renal disease, HTN, drugs (ASA, diuretics, cyclosporine, thiazides, frusemide)
    • Urate excreted from kidneys
Diagnosis
  • Based on aspirate showing negative bifringement crystals that are rod and needle shaped
  • CPPD crystals are weakly positive bifringement, rhomboid shape
  • Radiology: Soft tissue swelling, eccentric opacities, punched out erosions with sclerotic margins and overhanging edges. Can use dual energy CT to differentiate CPPD from urate, best utilised for inaccessible joints
 Management
  • Non-pharmacological: Rest, ice, compression, elevation
  • Pharmacological Mx of acute gout:
    • NSAIDs: need dose upper limit of normal, normal CIs for NSAIDS exist
    • Colchicine: disrupts microtubule fx --> low dose = high dose with less SE, use in acute situation, long term SE = neuromyopathy in renal impairment
    • Systemic corticosteroid = need 30 – 50mg for 5d, other option = depot ACTH (40mg IM)
    • Intra-articular corticosteroid = req technical competence, skin atrophy at site of inj, rapid onset of action, well tolerated
    • Canakinumab (IL-1b) in an RCT, good evidence coming, licensed in EU
    • Anakinra: IL-1R antagonist, shorter half life than canakinumab
  • Pharmacological Mx of chronic tophaceous gout
    • Symptom control/suppression – colchicine can be used 0.5mg daily
      • EMG/ NCS mild axonopathy, myoneuropathy risk,
    • low dose oral corticosteroids, evidence for IL-1 inhibition (anakinra, canakinumab) in trials. 
    • Reduce urate load, aim <0.36mM (treat to target):
      • Indication for Rx with hyperuricaemia + gouty arthritis (tophi, erosions, >2 attacks/yr, urate nephropathy, urate calculi), NOT Rx if asymptomatic and non of the aforementioned as toxicity too great and evidence of benefit lacking
    • Allopurinol inhibits xanthine oxidase, start low, dose 100 – 800mg. NOT TO BE USED WITH AZATHIOPRINE, renally excreted, risk of hypersensitivity [HLAB5801, occurs <6w into dose significant --> DRESS (Drug rash with eosinophilia and systemic symptoms + interstitial nephritis + hepatitis)
    • Feboxistat, now licensed, non purine analogue inhibitor of xanthine oxidase --> allopurinol allergy pts
    • Uricosouric agents --> effectively inhibit uric acid reabsorption in prox tubule [URAT1/ OAT4 inhibition] eg probenecid + losartan

Calcium Pyrophosphate Dihydrate Arthropathy
  • Risk factors: Age, female, metabolic [hypophosphataemia, hypomagnesaemia, hyperparathyroidism, OA, haemochromatosis, wilsons disease]
  • Presentation: There are a number of different presentations listed below (courtesy of BMJ best practice)
    • An acute, typically mono-articular inflammatory arthritis often affecting large joints such as the knee
    • A polyarticular inflammatory arthritis affecting large and small joints
    • A chronic polyarticular arthritis, characterised by superimposed acute attacks of inflammatory arthritis.
    • Osteoarthritis and CPPD without an inflammatory component
    • The chronic form of CPP arthritis mimics osteoarthritis or rheumatoid arthritis and is associated with variable degrees of inflammation
  • Dx: Effusion --> positive bifringement crystals (weakly), rhomboid shape, may miss
  • Radiology = chondrocalcinosis, esp meniscus
  • Rx: Joint aspirate, immobilization, NSAIDS, intra-articular and systemic steroids

Rheumatoid Arthritis


History
  • Natural Hx: 5 – 20% self-limiting polyarthritis; 5-20% minimally progressive disease, 60 – 90% progressive disease
  • Palindromic rheumatism, sudden onset, peaks within hours, usually large joints, no structural damage, important to recognise b/c Rx with hydroxychloroquine
  • Morning stiffness (ask if >60min)
  • All peripheral joints and cervical spine can potentially be affected
  • DIP joints NOT affected
  • Flexor and extensor tenosynovitis of hands
  • Tendon rupture (usually extensor)
  • Atlanto-axial instability in severe RA
  • Fatigue and weight loss
  • Extra articular symptoms include the following
    • Eyes: Sicca symptoms, scleritis, corneal ulcers
    • Skin: Ischaemic ulcers and digital gangrene, Rheumatoid nodules in Pts who are RF +ve
    • Lungs: Pleural effusions, nodules and ILD
    • Nerves: Compressive neuropathy (carpel tunnel), Mononeuritis multiplex
    • Lymphoma (B cell) 2-3 fold increase
    • Capillaritis
    • Felty's syndrome, triad of:(1) Neutropenia (2) Splenomegaly and (3) Deforming RA
Examination
  • For detail see Rheumatology short case section
  • General inspection:
    • Cushingoid
  • Rheum: Symmetrical deforming polyarthropathy of the small and large joints
  • Skin: Rheumatoid nodules, evidence of capillaritis
  • Lungs: effusions and fibrosis
  • Cardiac: pericardial rub
  • Abdomen: splenomegaly of Felty’s, Epigastric tenderness from ulcer/gastritis d/t prednisone or NSAIDs
  • Eyes: sicca, episcleritis, scleritis
Investigations
  • FBC: Anaemia of chronic disease
  • UEC: decreased renal function with secondary amyloidosis, order urine albumin: creatinine ratio to help quantify
  • CRP + ESR: Raised inflammatory markers
  • CXR: Pleural effusions (exudative) in 5% of Pts, low pH, very low glucose and RF+
  • Joint aspirate: Inflammatory fluid: WC 200 - 2000
  • Serology: RF positive in 70% of pts, predicts severe joint disease and increased likelihood of extra-articular features, Anti-CCP: similar sensitivity but greater specificity, adverse prognostic factor
  • Radiological features: (1) periarticular soft tissue swelling (2) deformities (3) joint subluxation (4) juxta-articular osteopenia (5) periarticular erosions (6) symmetrical joint space narrowing
  • MRI findings: looking for 3 things: synovitis, marrow oedema in bones surrounding inflamed joints (best predictor of development of erosions), erosions
Management
  • Goals: (1) Confirm Dx (2) Optimise symptoms (3) Prevent deterioration/ progression 
  • Simultaneous control of symptoms and retard progression of erosive disease, frequent monitoring to determine lack or progression of disease
  • Symptom control:
    • NSAIDS/ stronger analgesia/ corticosteroids/ local injection of corticosteroids
  • Retard progression: achieve remission [DMARDS = biological vs non-biological or traditional]
    • DMARDS: indicated if (1) New presentation AND active disease, start within 3/12 (2) seropositive disease (3) erosions on X-ray (4) clinical deformities
    • bDMARDS --> no remission despite 6/12 trial DMARDS
    • DMARDS improve cardiovascular mortality
  • Mild disease [defined by <6 joints + RF neg + non-erosive]
    • NSAIDS, if active then hydroxychloroquine [SE = visual field defects, scotomoas, colour blindness]/ sulfasalazine [SE = rash, gastrointestinal, aplastic anaemia, hepatitis – monitor LFTs frequently]
    • hydroxychloroquine requires yearly ophthalmologic reviews
  • Severe disease [> 6 joints, active synovitis, erosions, RF +, high ESR/CRP]
    • NSAID + Pred [bridge Rx until DMARDS take effect, slows radiology progression, decreases synovitis], + MTx [contraindicated in hepatic – 1/100 severe fibrosis Aus study 1994, renal, lung disease – bilateral alveolar infiltrates, hypoxia, decr DLCO, Rx pneumonitis --> pred 60mg 2-4/52 noting majority recover completely; those who can’t stop EtOH, LFTs monitored 1-3/12, use folic acid, risk of lymphomas --> reverses when ceased MTX]
    • If no response, increase MTX dose OR add 1 off [sulfasalazine/ hydroxychloroquine/ leflunomide --> inhibits DHODH which is needed for de-novo pyrimidine synthesis, activated T lymphocytes don’t have salvage pathway!, very long t/12 b/c enterohepatic re-circulation need cholestyramine washout, diarrhea (30%), peripheral neuropathy and ILD rare s/e/; NOT FOR use in pregnancy, cyclosporine]
  • Biologics
    • TNF-alpha --> [preRx screen for HBV/HCV/HIV/TB vaccinate pneumococcus + flu, No live vaccines 3 weeks before and up to 3 months after, Auto-abs esp for infliximab 40%, reason for Rx failure, give with MTX reduce prevelance of Abs, cases of demyelination syndrome exist, cancers = skin, small risk lymphomas]
      • If Mantoux/ IGRA + --> pretreat for 2/12 INZ then continue Rx for 9/12, TB usually presents with extra-pulmonary disease
    • Abatercept = CTLA4 bound to Ig, inhibitory co-stimulation to T cells. Give in combo with MTX, non inferior to TNFs, less infection risk esp in bronchiectasis
    • Tocilizumab = IL6R mab, prevents signaling down IL-6-IL-6R signal transduction, NO NEED FOR MTX, and only bDMARD monoRx > MTX monoRx, only biological agent approved for single use, > adalimumab in efficacy. SE = ALT/AST up, dyslipidaemia, opportunistic infections, bowel perf! --> contraindicated if have diverticulitis
    • Rituximab: Use only if RF+/ ACPA+, effective if MTX resistant + TNF-alpha failed, use if have infection or malignancy
    • Tofacitinib: small molecule inhibitor [works intracellularly] of janus-kinase-STAT pathway activation (JAK3,1 >2), PBS for monotherapy or combo with MTX, SE similar to tocilixumab
  • Treatment Algorithm: Dx then start NSAID + Prednisolone + MTX [leflunomide if MTX contraindicated] --> if no response 6/12 then biological or other DMARDS b vs non-b [decision based on poor prognosis markers such as RF+, ACPA+, erosions, high disease activity]
  • Pregnancy --> contraindicated are MTX, leflunomide, cyclosporine, cyclophosphamide + NSAIDS [PDA closure], can use hydroxychloroquine, sulfasalazine, azathioprine
  • Aggressively manage cardio-metabolic risk factors as chronic disease is associated with accelerated atherosclerosis
Picture

SLE


​General factoids
  • Female: male 10:1, decreases post menopause to 1:1, onset 15-40yo
  • Survival --> worst for hispanics, but even then 5yr = 87%
  • Etiology: Multifactorial and polygenic (STAT4, PTPN22), Complement defeciency (C1q = 90% chance of developing lupus!, C4), environ (smokers, UV, EBV), hormonal (VitD)
  • ACR criterion for Dx and other clinical features
    • Req 4 with 1 clinical [acute/ subacute/ chronic cutaneous lupus, oral ulcers, non-scarring alopecia, synovitis, serositis [pleural>pericardial, common problem!], renal = 500mg proteinuria or RBC casts, neurologic manifestations, anemia, leukopenia, thrombocytopenia] and 1 immunological [ANA (+ 95-99%), dsDNA (best for monitoring disease activity), DAT+, anti-Sm (most specific, remain + even in remission, assoc with renal and CNS disease), anti-ribosomal P10 (in Asia), phospholipid +, low complement]. Other immunology = SSA (neonatal lupus, congenital heart block, cutaneous) > U1RNP (myositis, raynauds) > SSB (neonatal lupus, cutaneous), CRP does not correlate with disease titre. 
    • Can Dx lupus if renal Bx proven without above criterion
​History
  • Protean manifestations with myalgia, malaise, fevers
  • Skin: can have ANA neg lupus as Ro-52 antigen not eluted with ANA, annular rash with central clearing = classic Ro-associated subacute cutaneous lupus
  • Arthritis/ arthralgia = most common clinical presentation, even nodules can happen, non –erosive but deforming, correctible = jacoud’s arthropathy
  • Lung involvement: pneumonitis, serositis, shrinking lung [diaphragmatic dysfx + pulm fibrosis], PE, pulmonary hypertension [ACA], pulmonary haemorrhage.
  • Heart: serositis, conduction block, liebmann-sacs vegetation [50% autopsy, assoc with ApL]
    • Accelerated atherosclerosis: 2-5x death, accelerated by prednisolone, statins for LDL >3, BP >130 --> ACE/ARB
  • Renal disease: worst prognosis, symptomatic only in advanced disease, need regular monitoring, bx if increasing creatinine with nil other cause OR proteinuria 1g OR protein 500mg + >5RBC/HPU OR protein 500mg + cellular cast
    • Class 1: minimal mesangial = normal LM, no Rx, ACE for proteinuria
    • Class 2: mesangioproliferative, no Rx, ACE
    • Class 3: focal prolif <50% Glomeruli, Rx indicated
    • Class 4: diffuse prolif >50% glomeruli, Rx indicated
    • Class 5: membranous, Rx if in nephrotic range
    • Class 6: advanced sclerosed --> >90% glomeruli sclerosed, no Rx, burnt out
  • Neurological: 5 commonest syndromes (1) headache (2) mood disorder (3) sz (4) cognitive dysfx = most common (5) cerebrovascular disease, MRI most useful [atrophy = commonest finding, look for increased signal intensity both white + grey matter], assoc with APL + anti-ribosomal P10
  • Antiphospholipid syndrome: [prior pregnancy loss OR prior thrombosis AND mod high titre of aCL, LAC , B2GP1 done 12/52 apart], primary or secondary [10-30% lupus pts], LAC = pregnancy worse, triple positive = lots of thrombosis
  • Neonatal lupus: Congenital heart block develops in 2-3% of mothers with SSA/SSB, 60% req pacemaker, 20% die; cutaneous lupus will clear by 6/12
Examination
  • Assess for steroid use: Cushingoid or prox myopathy
  • Rheum for Symmetrical, deforming polyarthropathy - reducible
  • Skin for alopecia or Rash
  • Lungs for fibrosis or effusion
  • Heart for pericarditis, murmur for liebmann-sacs endocarditis
  • Abdo for hepatosplenomegaly
Investigations
  • FBC: chronic anaemia, macrocytocis if MTX is used, DAT for evidence of haemolytic anaemia
  • UEC: raised creatinine, urinalysis, casts, microscopy for casts, glomerular red cells, proteinuria
  • C3/ C4 levels - active disease associated with complement consumption. Also complement deficiency adverse prognostic marker
  • CRP: not correlated with disease activity but if elevated means that the inflammation is arising from somewhere else
  • ESR
  • ANA: elevated in >95% of SLE, can have ANA negative lupus in chronic cutaneous lupus with Ro-52+, ENA +, dsDNA (correlates with disease titre), anti-Sm more specific, not correlated with disease titre, anti-phospholipid antibodies, U1-RNP associated with mixed connective tissue disease
  • Renal biopsy
  • Imaging of joints for arthropathy
Management
  • Goals: Confirm Diagnosis, Optimise Symptoms, Prevent Deterioration, Manage Exacerbations
  • Symptom managment
    • NSAIDS for arthralgia, synovitis, constitutional symptoms
    • Avoid sun exposure/ use sunscreens
    • Stop smoking
  • All patients should be on hydroxychloroquine
    • S/E = maculopathy after prolonged use, more common in renal dysfx, irrerversible if get bull’s eye maculopathy, screening at baseline then annual opthal assessment
  • Corticosteroids: initial control for inflammation
  • MTX --> arthritis, skin rash, constitutional sx
  • Leflunomide --> arthritis, or if methotrexate is contra-indicated
  • cyclophosphamide --> major organ involvement
  • Renal: Treat 3,4, 5 agressively.
    • Class 3 & 4 induction: MMF for 6/12 [Hispanics/ afro-americans] OR cyclophosphamide [500mg 2nd weekly x 6 esp whites] AND Pred [1g x 3 pulse then taper 0.5-1mg/kg/d]; Maintainence [AZA or MMF]
    • Class V --> Rx if nephrotic [>3g/d] with MMF + Pred, no improvement in 6/12 --> cyclo
  • Neuropsychiatric lupus: Cyclophosphamide + corticosteroids
  • APLS --> thrombosis = INR 2-3 indefinitely, if thrombosis on warfarin then INR 3-4 OR INR 2-3 + aspirin, no evidence for NOACS yet, no role for immunosuppressant, in pregnancy use aspirin + LMWH
  • Pregnancy --> no active disease then monitor, mild disease --> hydroxychloroquine, severe disease --> pred, lupus nephritis --> pred/ AZA if necessary.
    • Note mycophenylate can not be used in pregnancy, but if planning to be pregnant mycophenylate as induction better than cyclophosphamide
    • Advice patient to take prophylactic pregnancy preventative measures if active disease
    • Note that 60% relapse when pregnant
    • Risks of worsening renal function
    • Risk of neonatal lupus
  • Rituximab --> Rx resistant disease; seems to be race related [better in afros and Hispanics]
  • Belimumab --> blocks BLyS [survival cytokine upregulated in active lupus], evidence accumulating

Seronegative spondyloarthropathies


Ankylosing spondylitis

Epidemiology and general factoids
  • Inflammatory arthritis of the axial skeleton with extra axial and extra articular involvement
  • Progressive stiffening and fusion of the spine
  • Strong association with the HLA B27 gene, 90 - 95%, 0.5 - 1% pop suffer from AS, male: female 3:1, 5% of population have HLA B27
  • Often there is a 9 yr delay to diagnosis
Clinical features
  • Inflammatory back pain:
    • Insidious onset
    • improvement with exercise
    • No improvement with rest
    • Nocturnal pain that improves on walking
    • (Responds to NSAIDs)
  • Buttock pain – often alternating, poorly localized (sacro-ilitis)
  • Restriction in spinal movement
    • Characteristic posture
    • All segments of spine have reduce movement
    • Chest expansion reduced (costo-vertebral joints)
  • Final stage of AS with severe kyphosis of thoracic and cervical spine
    • Straightening of cervical lordosis
    • Exaggeration of thoracic kyphosis
    • Straightening of lumbar lordosis
  • Hip involvement as well in this patient: Fixed flexion deformity of both hips
  • Extra-articular manifestations
    • anterior uveitis - painful red eye, photophobia, blurred vision, with recurrence a problem. Can be a HLA B27 associated disease without ankylosing spondylitis
    • Inflammatory bowel disease - 70% have microscopic subclinical asymptomatic colitis
    • Osteopenia
    • Cauda-equina, cervical myelopathy
    • Fractures
    • Cardiac: CVD risk, aortic regurgitation, conduction disturbance, accelerated atherosclerosis
    • Respiratory: chest wall restriction, apical fibrosis (apical fibrosis is usually asymptomatic, chest wall restriction is more common cause of symptoms)
    • Secondary amyloidosis
Investigations
  • Image SI Joints: If sacroilitis present then it significantly increases the likelihood of spondyloarthritis
    • Early changes: erosions, sclerosis at joint margins
    • Later: pseudo-widening of joint (combination of erosions)
    • Last: joint space narrowing progressing to ankylosis
    • Need to demonstrate Sacroilitis to obtain Rx with biological agents
  • Cervical and thorac-lumbar spine:
    • Vertebral squaring: due to erosion at corners of the vertebral bodies (where annulus fibrosis attaches) -> this can develop into a Romanus lesion with sclerosis of the bone (compare to one above)
    • Syndesmophyte
  • MRI in spondyloarthritis: Bone marrow oedema, erosions are detected earlier
Management
  • Physiotherapy/exercise program and NSAID
    • May be effective in preventing radiographic progression
    • Need to have had trial of physiotherapy and NSAIDS to escalate to biological agents (trial for 3 months)
  • Axial disease
    • After NSAID/Exercise -> next step is TNF blockers (no evidence for other disease modifying drugs)
    • Local corticosteroids can be useful for sacro-iliac disease or troublesome facet disease
  • Peripheral disease
    • Sulfasalazine for peripheral arthritis (but no evidence for other disease modifying agents)
    • Local corticosteroids can be useful
    • TNF inhibitors (infliximab/etanercept/adalimumab): 70-90% get improvement in symptoms
  • TNF inhibitors
    • Previously thought that despite being fantastic for symptoms did not affect radiographic progression
    • Recent prospective longitudinal study in 330 patients found
      • TNF inhibitor use was associated with less radiographic progression
      • Early initiation and longer duration of tratment seemed more protective

Psoriatic arthropathy

Clinical Features
  • 5 distinct patterns of arthritis
    • Asymmetric oligoarthritis/monoarthritis
    • Polyarthritis – symmetric
    • Spondylo-arthritis – axial, AS like
    • Distal interphalangeal joint with nail disease
    • Arthritis mutilans 
  • Skin disease
  • Dactylitis – ‘sausage digit’
  • Enthesitis
  • Nail changes more common
Investigations
  • Classic radiological involvement: juxta-articular involvement, pencil in cup deformity
Management
  • Physiotherapy, multi-modal analgesia, NSAIDS
  • Avoid systemic steroids because rapid wean of topical steroids can cause flare of skin disease
  • DMARDS (methotrexate, sulfasalazine and lefluoamide) used for peripheral disease 
  • Biological agents are anti-TNF agents

Systemic Sclerosis


Epidemiology of scleroderma:
  • Rare disease, female > male, age of onset 40 – 60, limited > diffuse, environmental toxins implicated
  • FHx strongest RF, but still very small
Generic symptoms
  • Arthralgia 98% reported [erosive in 25%]
  • Legs: ulceration, vasculitis
  • Tenosynovitis with tendon friction rub --> worse prognosis
  • Myalgia --> may have biopsy fibrosis secondary to disease
  • GIT --> eosophageal hypomotility, GAVE, poor prognostic indicator
  • Lung disease:
    •  ILD, lung fibrosis is cause of death usually
    • DLCO<50 assoc with worse prognosis and assoc with pulm HTN, progression occurs early in on the course of the disease [first 5y], Scl70 predictor of getting disease, anti-centromere protective
    • Histology = NSIP (90%)> UIP [worse] pattern, in fact HRCT is the most powerful predictor of mortality
      • Dx --> HRCT, DLCO, 6 min walk test
      • Rx --> cyclophosphamide for 12/12, BMTx trials St Vincents, RPAH
  • Cardiac disease
    • fibrosis, conduction deficits, coronary spasm, assoc with diffuse disease + Scl-70, effusions in 30 – 40%
  • Renal disease:
    • hypertensive crisis, secondary to microvacular changes, assoc with RNA polymerase antibodies, renal crisis assoc with HTN + oliguric renal failure, use ACE-inhibitors
  • Scleroderma classification
    • Localised – morphea
    • Limited scleroderma: long Hx raynauds, scleroderma distal to knees and elbows, anywhere else = diffuse, lung disease --> pulmonary HTN + digital ischaemia > ILD, cardiac and renal disease rare, Antibodies = centromere, nucleolar and speckled, if centromere + --> decreased risk of ILD + pulm HTN
      • CREST syndrome
    • Diffuse scleroderma: recent onset raynauds, skin disease rapid, renal and cardiac involvement, lung disease ILD > Pulm HTN, antibodies Scl70 (predict lung) and RNA polymerase (1 in 8 will have renal crisis)
      • Skin disease pattern --> rapid progression of skin change, plateu, skin soften and can go back to normal skin
      • DDx eosinophilic fasciitis, here fingers are spared cf scleroderma, assoc with orange peel skin,
  • Nailfold capillaroscopy --> dilated loops + areas of drop out consistent with scleroderma/ Dermatomyositis pattern
  • Stem cell Tx --> case reports show complete resolution, disease progression 10%, most have 60-70% improvement
    • Smokers no benefit from Rx, need careful screening as mortality mainly from cardiac causes
Pulmonary Hypertension in scleroderma
  • Occurs in 12% of patients with both limited and diffuse disease
  • Later complication: 5-10 years of duration of disease
  • High mortality
  • Dx
    • Suspect in patients with DLCO < 50% and minimal fibrosis on HRCT --> ECHO
    • ECHO: pulm pressure >50  --> right heart cath
    • Mean pulmonary artery pressure > 25mmHg with PCWP < 18mmHg
      • Mean PAP on exercise > 30mmHg with wedge < 18mmHg
  • Rx
    • Warfarin 
    • Mainstay now is combination therapy include endothelin antagonists, PDE5 inhibitors and prostaglandins but single agent therapy only subsidized in Australia, and must show clinical stability in 6/12 for ongoing Rx
      • Ambrisentan + tadalafil cf monotherapy reduced Rx failure by 50% in particular hospitalisations
    • Rx only subsidized for WHO functional class III or IV
Management of Raynaud's
  • Keep warm
  • Dont smoke
  • Topical nitrates
  • Calcium channel blockers
  • prostacyclin infusions if severe
  • digital sympathetctomy if severe
Management of skin disease
  • Physiotherapy
  • Some evidence for stem cell transplant and cyclophoshomide. 
  • For diffuse skin thickening MMF/ MTX. Evidence for MTX in particular for early skin involvement from obesrvational studies therefore the evidence is relatively weak. Evidence for mycophenolate even weaker with small observational studies supporting its use. 
  • IVIG/ rituximab may be trialled in refractory cases
Management of gastrointestinal disease
  • Facial thickening and decreasing diameter of oral apeture - exercises
  • oesophageal hypomotility management aims at diminishing risks of gastrointestinal reflux disease, managing strictures
  • consideration for prokinetic agents such as metoclopramide
  • small bowel bacterial overgrowth Rx with oral antibiotics
  • pancreatic insufficiency --> Rx with pancreatic enzyme replacement
Management of arthritis
  • Physiotherapy to limit joint immobility
  • Simple NSAID based analgesia
  • if inflammatory - consider glucocorticoids
  • add hydroxychloroquine 200 - 400mg daily
  • If not controlled consider methotrexate
Management of cardiac disease
  • Pericarditis - normal management as per guidelines (colchicine + high dose NSAIDS)
  • may develop cardiac tamponade physiology quickly - and with no chest pain
  • Heart failure associated with reduced systolic ejection fraction is treated with standard heart failure treatments, such as angiotensin-converting enzyme (ACE) inhibitors, implantable-cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT
  • While there are no established treatment practices for myocarditis associated with SSc, immunosuppressive agents are typically used in a manner comparable to that for the treatment of interstitial lung disease associated with SSc.

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