RA + Spondyloarthropathy Flashcards
Dactylitis is a marker of disease severity in which condition?
Psoriatic arthritis
What joints dose RA affect?
Usually the small joints of the hands (MCP, PIP), sparing the DIPS. Can also affect larger joints like knee/ankle but they occur later. Can also affect atlantoaxial joint
What are the classic hand signs of RA?
- Radial deviation of wrist
- Ulnar deviation of fingers at MCPs
- Swan neck deformity: flexion at DIP, hyperextension at PIP
- Boutonniere deformity: flexion at PIP, hyperextension at DIP
- Z deformity of thumb: Z deformity of thumb (Hitchhiker thumb): IP hyperextension and MCP flexion
Extraarticular manifestations of RA
- Skin: rheumatoid nodules, vasculitis, raynaud phenomenon
- Lung: pulmonary nodules (related to subcutaneous rheumatoid nodules), pleural effusion, interstitial lung disease
- Ophthal: episcleritis, scleritis
- Neuro: carpal tunnel, cervical cord compression
- Cardio: premature atheroscleroris, CAD, PVD
- Felty Syndrome: triad of RA, neutropenia, splenomegaly
- Lymphoma (3x risk)
What patterns of ILD are associated with RA?
UIP: usual interstitial pneumonia - subpleural reticulation, apical basal gradient, traction bronchiectasis, honeycombing
NSIP: non specific interstitial pneumonia
- subpleural sparing, traction bronchiectasis, apical basal traction, ground glass changes
Characteristics of felty syndrome
- Felty syndrome-in longstanding, sero+, nodular, deforming RA
- Splenomegaly, leukopenia, lower limb ulceration, hyperpigmentation, bone marrow hyperplastic suppressed by ongoing inflammation
- Triad: chronic arthritis + neutropenia + splenomegaly
- Associations
Extra-articular features including nodules, lymphadenopathy, leg ulcers
HLA-DR4 - BM: normal myelopoiesis, maturation arrest
- ↑ susceptibility to infection
- ↑ risk of lymphoproliferative disease
- Treatment
Aggressive RA treatment
G-CSF or GM-CSF
What conditions is HLADR4 associated with?
RA
Addison disease
Type 1 Diabetes
(RAD/ADR)
What increases the genetic predisposition for RA
HLADR1
HLADR4 (main one)
HLA-DRB1-04
Environmental factors of RA
- Smoking - increases the risk in seropositive RA
- Hormones: OCP decrease risk of RA especially ACPA positive disease
- Periodontal disease: Prophyromonaas gingivalis 4x increased risk of RA
RF and anti-CCP in RA
Anti-CCP
- Highly specific 95%
- Precede onset of RA and an important predictor for the development of RA
- Associated with more severe and destructive disease and associated with RA related ILD, CVD
- Better predictor of erosive disease
- Presence means increased change of responding to rituximab following failure of anti-TNFa therapy
RF
- An antibody (usually IgM) directed against Fc portion of humanIgG
- Seropositive patients = more severe clinical disease, more complications, increased cardiac risk
- Can decrease/seroneg with effective treatment
- Better predictor of extra-articular manifestations
Neither RF or anti-CCP are helpful to assess currrent RA activity
What non-RA situations is RF associated with?
- Sjogrens (75-95%), cryoglobulinemia (40-100%), SLE (15-35%), other autoimmune diagnosis
- Non-rheumatic: indolent/chronic infection (Hep B/Hep C, TB), malignancy
- Very high titre consider:
Cryoglobulinaemia
Primary sjogren’s syndrome
Xray findings of RA
- Symmetric involvement
- Periarticular Soft Tissue Swelling (joint effusion, tenosynovitis)
- Joint Space Narrowing ← Pannus + MMPs
- Bony Erosions/Marginal erosions ← Pannus + Osteoclasts
- Periarticular Osteopenia/Juxtaarticular osteoporosis ← RANKL + Osteoclasts (periarticular osteopenia often early xray sign)
- Deformities + Subluxation in advanced disease
Early x-ray findings
loss of joint space
juxta-articular osteoporosis
soft-tissue swelling
Late x-ray findings
periarticular erosions
subluxation
Benefits of US and MRI in RA
US
- Greater sensitivity to detect synovitis
- Power doppler to detect inflammatory activity
- Early detection of cartilage and bone structural damage
- Multiple joints affected
MRI
- Detailed info regarding synovitis, marrow oedema (precursor to erosions) and erosions
- Limited one joint per exam
Joint aspirate of RA
- Opaque/Translucent
- High Protein ← Inflammatory Exudate
- Moderately High Neutrophil Count ← Due to Complement Activation (c5a)
- Mildly Low Glucose ← Consumption by Inflammatory Cells
- Low Viscosity ← Neutrophilic Enzymes/MMPs break down hyaluronic acid
- Negative Culture & Polarising Microscopy
↑ Proteins & Neutrophils but ↓ Glucose & Viscosity
Histopathological features of synovial biopsy in RA
Pathophysiology
- Synovial lining hyperplasia with underlying granulation tissue
- Lymphohistiocytic Infiltrate → B & T Cells, Plasma Cells, Macrophages
- Hypervascularity → Vasodilation + Angiogenesis
- Sparse Fibrinopurulent Exudate ← Fibrin + Dead Neutrophils
- Increased Osteoclastic Activity in Underlying Bone
- Neutrophils NOT found in synovium but in synovial fluid
- Osteoclastic activity in the underlying bone → allows pannus to penetrate into the bone and cause juxta-articular erosions, subchondral cysts and osteoporosis
- Involves a genetic predisposition to RA in addition to environmental factors
- Genetic Predisposition + Hormonal Factors (Estrogen)
- Environmental Exposure → Infection + Smoking
- Loss of Self-Tolerance
- Autoreactive CD4+ T Cell
- Stimulate Autoreactive B Cell → Plasma Cell
- Plasma Cells produce Auto-antibodies → RF + Anti-CCP
- Immune Complex Formation
- Deposition into the Synovial Cavity
- Trigger Inflammatory Response by activating Complement + Macrophages
- Macrophages release IL-1, IL-6 & TNF-a
- Inflammatory Cytokines activate Fibroblastic Release of MMPs & RANK-L
▪ Matrix metalloproteinases (MMPs) are a group of enzymes that in concert are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue turnover.
▪ RANKL induces the differentiation of monocyte/macrophage–lineage cells into the bone–resorbing cells called osteoclasts - RANK-L stimulates Osteoclast Production & Activity → Bone Erosions
- Complement (c5a) draws in Neutrophils
- Inflammatory Cells + Granulation Tissue + Synovial Hyperplasia = Pannus
▪ Pannus = Mass of synovium and synovial stroma consisting of:
▫ Inflammatory cells → Neutrophils + Macrophages + Lymphocytes
▫ Granulation Tissue
▫ Synovial fibroblasts
▪ This grows over the cartilage and causes cartilage and bone erosion - Pannus ultimately chews away the cartilage and eventually into the bone
Treatment of RA
- 1st Line: NSAIDS + steroids + DMARDs (MTX)
MTX is the mainstay treatment
Patients unable to take MTX may require an alternative agent, such as HCQ, SSZ, or LEF. - 2nd Line: In patients resistant to initial DMARD therapy (eg, MTX), treat with a combination of DMARDs (eg, MTX plus SSZ and HCQ, or MTX plus a TNF inhibitor)
- 3rd Line: If failing above treatment then biological DMARD or tsDMARD (eg: JAK inhibitors)
Examples of biological dmards
- TNF-alpha inhibitors: Etanercept, Infliximab, Adalimumab
- T cell costimulation inhibitor (CD80/86): abatacept - soluble fusion protein consisting of CTLA-4 linked to IgG, blocks CD80/86
- IL-6 receptor antagonist: Tocilizumab
- IL-1 receptor antagonist: Anakinra
- JAK Inhibitors: Baricitinib (Jak 1,2), Tofacitinib (Jak 1,3), Upadacitinib (Jak 1)
- Anti-CD20 (B cells): Rituximab
Will need to screen for TB risk factors and perform quantiferon, may require prophylactic isoniazid
All BDMARDs are more efficacious when combined with conventional DMARDs
What medications do you avoid giving with methotrexate?
Trimethorpim +/- sulfamethoxazole due to risk of myelosuppression
MOA and SE of methotrexate
ANCHOR DRUG FOR RA
MOA:
Methotrexate inhibits dihydrofolate reductase, preventing the reduction of dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4), leading to nitric oxide synthase uncoupling and increased sensitivity of T cells to apoptosis, thereby diminishing immune responses. reduce PURINE SYNTHESIS
nausea, oral ulcers, hair loss, abnormal LFTs, cytopenias, risk of pneumonitis (increases with prior ILD), teratogenicity (needs to be held for 3 months prior to attempting conception) - preventable by prophylactic folates
Main SE
- hepatitis
- pneumonitis - can occur at any stage in treatment
- myelosuppression
Contraindication
- pregnancy
- alcoholism, liver disease
Note: subcut methotrexate more effective than oral
For cytopenias - folinic acid
Can be used prior to surgery, don’t need to stop
Sulfasalazine in RA and SE
- Useful when methotrexate contraindicated, eg: regular alcohol intake
- Reduces radiographic
- AEs:
Hypersensitivity reactions (mainly cutaneous), nausea, diarrhea, agranulocytosis, drug-induced lupus, azoospermia, hepatitis, pneumonitis, aplastic anaemia, haemolytic anaemia
SE: skin reactions (can cause DRESS), hepatitis, pneumonitis, agranulocytosis, aplastic anamiea
- Fever, rash, deranged LFTS - stop drug and do not rechallenge.
- The most common DMARDs to lead to AE within triple tx(mtx, ssz, hcq) regimens
Can be used in pregnancy
SE
- Oligospermia
- Steven Johnson Syndrome
- Pneumonitis
- Myelosuppression
- May colour tears - stained contact lenses
- Hepatitis
Cautions
- G6PD deficiency
- Allergic to aspirin or sulphonamides (cross reactivity)
Hydroxychlorquine in RA and SE
- Best tolerated DMARD but modest clinical defect
- No effect on radiographic progression
- First line treatment for palindromic rheumatism
- AEs
Hyperpigmentation
Retinopathy/Maculopathy
Bulls eye retinopathy - may result in severe and permanent eye loss - Limit dose to 5mg/kg
- Baseline ophthalmology exam within first year, annual screening after 5y
- Risk factors: high dose/duration of treatment; renal disease; pre-existing retinal disease; concomitant use of tamoxifen
Rarely: myopathy, cardiomyopathy
Lefluonmide in RA and SE
- Inhibits pyrimidine synthesis
- Slow radiographic progression
- AE: diarrhoea, hypertension, pneumonitis, teratogenic, peripheral neuropathy
- CI: pregnant + breast feeding, liver disease, haem abnormalities
Conjugated and excreted renally and in the gut
Extensive enterohepatic circulation = long half life
Require cholestyramine for washout
- Long half life 2 weeks
leflunomide has a very long wash-out period of up to a year which requires co-administration of cholestyramine
When is TNFi used in RA?
Effective in MTX incomplete responders
More effective when combined with methotrexate
Which TNFi is safe in pregnancy?
Certolizumab: lacks an Fc fragment, very little crosses the placenta
Can also use other TNFi
SE of TNFi
- Infections
- Opportunistic infections, eg: TB
Usually present as extrapulmonary manifestations, eg: weight loss - Malignancies - non melanoma skin cancer, lymphoma
- Demyelination especially etanercept
- Autoantibodies - ANA/ds DNA
Highest in infliximab, lowest in etanercept + certolizumab, methotrexate prevents antibody formation - Hepatotxocity
- Dermatologic reactions
- Lupus like syndromes
- Uncommon: psoraisis, vasculitis, sarcoidosis, drug induced lupus
Common to reactivate latent TB or hep B .
Abatacept in RA
- T cell costimulation inhibitor (CD80/86) - CTLA bound to Ig binds to B7
- Effective in MTx incomplete responders - approved in combination with Mtx
- Similar efficacy to TNFi
- More effective if anti-CCP positive
- Slows radiographic progress
- Lower risk of infections compared with TNFi and IL6 so may be safer in patients with infections such as bronchectasis
CTLA-4 Ig: inhibits binding of CD28 to CD80/86
Prevents T cell receiving co-stimulatory signal
SE: headaches, nausea, increased infections (but better than other bDMARDs), increased risk of haematological malignancies, exacerbates COPD
Tocliziumab in RA and SE
- IL6 inhibtior
SE:
- LFT changes,
- neutropenia,
- hyperlipidaemia (CV risk not increased),
- intestinal perforation (avoid in diverticulosis)
Rituximab in RA and SE
B cell inhibitor
Greatest benefit in seropositive patients
SE: infections, PJP, progressive multifocal leukoencephalopathy (PML), reactivation of hep b, diminished response to vaccinations
Avoid in Hep B
Effective in rheumatoid lung disease
JAK inhibitors in RA and SE (targeted synthetic DMARD)
Work in the cell nucleus
JAK: cytoplasmic tyrosine kinases, crucial for signal transduction to the nucleus from membrane receptors for cytokines
- Initiating players of JAK/STAT pathway
- Binding of effector molecules to JAK –> signal transduction to nucleus
Tofacitinib (Jak 1,3)
Baricitinib (Jak 1,2)
Upadacitinib (Jak 1)
More effective than adalimumab (TNFi) in methotrexate resistant RA
SE:
- Risk of thrombosis, appears higher for baricitinib
- High risk of shingles
- Similar to IL6 inhibitor: LFT changes, neutropenia, hyperlipidaemia, lower intestinal perforation
- Cytopenia including anaemia
- Malignancies
- Sudden CV risk
Jak1 : most important in RA
Jak 2: thrombosis
Jak3: cytopenias
In which situations should the following biologics be avoided: TNFi Tocilizumab Rituximab JAK inhibitors
- TNFi: MS or family history of MS
- Tocilizumab: diverticulitis
- Rituximab: Hep B infection
- JAK inhibitors: thrombosis/vte, zoster
In which situations would the following biologics be favoured?
TNFi
Rituximab
Abatacept
- TNFI: pregnancy, history of treated malignancy
- Rituximab: past or current lymphoma, past serious infections, MS
- Abatacept: past serious infections
What medications should be trialled in TNFi insufficient responders?
- Abatacept: T cell costimulation inhibitor CD80/86
- Rituximab CD20
- Tofacitinib JAK 1/2/3 inhibitor
Vaccinations before commencing biological DMARD
- Pneumovax and annual flu vaccine
- For JAK inhibitor
Zoster: as live vaccine need to wait 4 weeks before commencing, safe to administer with pred < 20mg/daily and conventional dmard - Rituximab: associated with impaired vaccination response, need to administer 6 months after last infusion
If live vaccine needs to be administered while on bDMARD - WH for 4 weeks, administer vaccine, resume after 4 weeks
- Vaccinate for Hep B, pneumococcus, fluvax
- No live vaccines (yellow fever, MMR, BCF, VZV) on biologicas or MTX or Arava or Pred >10mg)
DMARDs and pre-operative management
- Stress dose corticosteroids
- Methotrexate: WH 1 week before surgery (risk of toxicity if patient develops post op AKI
- BDMARD: WH one treatment cycle, resume 2 weeks post op
What is the effect of RA on fertility?
- Longer time to pregnancy for RA women trying to conceive
- Associations: increased age, nulliparity, disease activity, preconception use of NSAIDs and pred >7.5
- NSAIDs used near time of conception/early pregnancy may interfere with implantation
Effects of pregnancy on RA
- Reduced RA activity during pregnancy
- 90% will flare during post-partum period usually within the first 3 months
What DMARDs can be used during pregnancy?
- TNFI are safe, but consider stopping at 30-32 to decrease passage across placenta - certolizumab is still safe to continue
- Infants exposed to TNFi in utero should not receive live vaccines for first 6months of life (eg: rotavirus)
Low risk during pregnancy: hydroxychoroquine, sulfasazline, pred <10mg/daily, azathioprine, cyclosporin, tnfi
High risk: methotrexate, lefluonmide
Cardiovascular disease in RA
RA is an independent risk factor for cardiovascular disease
What are poor prognostic factors for RA
- Sustained high levels of synovial and systemic inflammation
- RhF and/or ACPA titre
- Early erosions on imaging studies
- Other
Extra-articular features: ILD, nodules
Smoking
Poor education, decreased socioeconomic status
HLA-DRB1*04 homozygosity (shared epitope)
Poor prognostic features rheumatoid factor positive anti-CCP antibodies poor functional status at presentation X-ray: early erosions (e.g. after < 2 years) extra articular features e.g. nodules HLA DR4 insidious onset
What is palindromic rheumatism
- Palindromic rheumatism (PR) is a rare type of inflammatory arthritis. Between attacks of joint pain and swelling, the symptoms disappear, and the affected joints go back to normal with no lasting damage.
- Sudden onset, peaks within hours and lasts 24-48 hours.
- Can involve single or multiple joints, does not cause joint destruction and similar predisposing genetic risk factors to RA
- Treat with hydroxychloroquine to reduce risk of progression to RA
What is remitting seronegative symmetric synovitis with pitting oedema (RS3PE)
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is an acute-onset disorder in the elderly, characterized by symmetrical synovitis with pitting edema of the dorsum of the hands and feet (“boxing glove appearance”, and is a known paraneoplastic syndrome
Tenosynovitis +++
Good response to steroids
RF + Anti CCP negative
Where does RA affect the spine.
Affect the cervical spine early in the course of disease causing atlantoaxial sublaxation.
Can cause cervical radiculopathy and cervical cord compression
What contributes to mortality in RA?
Cardiovascular disease - RA is an independent RF for cardiovascular disease
Which medications are unsafe and safe in pregnancy?
- methotrexate is not safe in pregnancy and needs to be stopped at least 6 months before conception
- leflunomide is not safe in pregnancy
- sulfasalazine and hydroxychloroquine are considered safe in pregnancy
- low-dose corticosteroids may be used in pregnancy to control symptoms
- NSAIDs may be used until 32 weeks but after this time should be withdrawn due to the risk of early close of the ductus arteriosus
Mechanism of action fo methotrexate
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines.
Diagnostic criteria for ankylosing spondylitis?
- Chronic back pain for at least 3 months and age of onset < 45 years and either
- Sacroiliitis on imaging and at least 1 SpA feature or HLA-B27 positive and at least 2 other SpA features.
SpA features
- Inflammatory back pain
- Arthritis
- Enthesitis
- Uveitis
- Dactylitis
- Psoraisis
- Crohn’s/colitis
- Good response to NSAIDs
- Family history of SpA
- Elevated CRP
What are features of inflammatory back pain.
- Age of onset <40
- Insidious onset
- Night pain (with improvement upon getting up)
- Improvement with exercise
- No improvement on rest
- Alternating buttock pain
Clinical manifestations of ankylosing spondylitis.
- Axial features
Inflammatory back pain, buttock pain (often alternating indicating sacroiliitis), restriction of spinal movements (characteristic posture, reduced RO and chest expansion) - Extra-axial MSK features: peripheral arthritis that is usually asymmetric oligoarthritis of LL and enthesitis (30-50%) tends to affect heel, dactylitis.
- Extra-articular features
Anterior uveitits (unilateral)
IBD, psoriasis, apical fibrosis, aortic regurgitation, AV block, IgA nephropathy, amyloidosis (long standing)
Ankylosing spondylitis features - the 'A's Apical fibrosis Anterior uveitis Aortic regurgitation Achilles tendonitis AV node block Amyloidosis
How do you test for SIJ pain?
- FABER test: pain in the ipsilateral SIJ on flexion, abduction and external rotation indicates positive test.
- Mennel Sign: Tenderness to percussion and pain on displacement (distraction) of the SIJ indicates sacroiliitis or degeneration.
Ways to test for reduced spinal mobility in advanced/severe AS.
- Schober test: lumbar forward flexion, increase of <4cm suggests impaired spine flexion.
- Decreased chest expansion
- Kyphosis
Findings of sacroiliitis on xray.
Characteristic findings (usually symmetrical)
Takes months to years to evolve - limited use in very early disease
Evident in 30-40% of those with disease duration 0-3 years
- Early Changes: erosions, sclerosis at the joint margins without alterations in the joint width
- Later: pseudo widening
- Last: joint space narrowing progressing to ankylosis
Ankylosing spondylitis - x-ray findings: subchondral erosions, sclerosis
and squaring of lumbar vertebrae
Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the diagnosis. Radiographs may be normal early in disease, later changes include:
- sacroiliitis: subchondral erosions, sclerosis
- squaring of lumbar vertebrae
- ‘bamboo spine’ (late & uncommon)
- syndesmophytes: due to ossification of outer fibers of annulus fibrosus
- chest x-ray: apical fibrosis
If the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS remains high, the next step in the evaluation should be obtaining an MRI. Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and prompt further treatment.
Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and ankylosis of the costovertebral joints.
Typical x-ray changes of the spine ankylosing spondylitis.
- Loss of lumbar lordosis
- Squaring of the vertebrae
- Syndesmophytes between adjacent vertebral bodies
- Shiny corners sign (Romanus lesion): reactive sclerosis of the superior and inferior margins of the vertebrae indicating site of new bone formation. -
- Dagger sign: ossification of supraspinous and interspinous ligaments produces a dense line projecting through the vertebrae.
- Bamboo sign: ossifcation of outer fibers of the annulus
Signs of sacroiliitis on MRI
Bone marrow oedema at vertebral corners
Erosions, spondylodiscitis
Management of ankylosing spondylitis.
- Exercise program
- NSAIDs
- DMARDs: sulfasalzine, methotrexate
- TNFA blocker: adalimumab, infliximab, golimumab, etanercept - rapid and sustained effect. Beyond 2 years of exposure, evidence to prevent radiographic progression.
- IL-17A blocker: Secukinumab
- Surgery
To qualify for biologic therapy, must have failed 12 weeks of NSAID and exercise and still have active disease.
Smoking and high disease activity predicts xray progression.
Predictors of response to biology therapy in ankylosing spondylitis.
- Shorter disease duration
- Young age
- Higher baseline inflammatory markers
- Worse inflammation on baseline MRI
- Less functional impairment
- HLAB27
Complications of ankylosing spondylitis.
- Complete fusion of spine - severely limited mobility
- Increased risk of OP - pathological fractures and possibly spinal cord injury
- Chalk stick fractures: transverse fractures through the fused spinal column caused by reduced flexibility due to a fused spine and OP
- Restricted chest expansion
- Apical fibrosis
Ankylosing spondylitis
- Male:Female Ratio
- Peripheral arthritis
- Enthesitis
- Skin lesions
- Sacroilitis
Ankylosing spondylitis
- Male:Female Ratio - more common in males
- Peripheral arthritis - uncommon asymmetric LL oligoarthritis
- Enthesitis - common
- Skin lesions -nil (10% have psoriasis)
- Sacroilitis - universal, symmetric
- HLAB27
Reactive arthritis
- Male:Female Ratio
- Peripheral arthritis
- Enthesitis
- Skin lesions
- Sacroilitis
Reactive arthritis
- Male:Female Ratio - 5:1 sexually acquired
- Peripheral arthritis - common asymmetric LL olgioarthritis
- Enthesitis - very common
- Skin lesions - circinate balinitis (serpiginous ring-shaped dermatitis of the glans penis), keratoderma belnorrhagica (plaques found on palms and soles)
- Sacroilitis - 40-60% often asmmetric
Psoriatic
- Male:Female Ratio
- Peripheral arthritis
- Enthesitis
- Skin lesions
- Sacroilitis
Psoriatic
- Male:Female Ratio - 1:1
- Peripheral arthritis - common, small and large joint asymmetric
- Enthesitis - common
- Skin lesions -Psoriasis
- Sacroilitis - 20% often asymmetric
IBD associated arthritis
- Male:Female Ratio
- Peripheral arthritis
- Enthesitis
- Skin lesions
- Sacroilitis
IBD associated arthritis
- Male:Female Ratio - 1:1
- Peripheral arthritis - common asmmetric LL oligoarthritis
- Enthesitis - uncommon
- Skin lesions - erythema nodosum, pyoderma gangrenosum
- Sacroilitis - ~20% with sacroilitis
In which spondyloarthropathy is peripheral arthritis predominant?
Reactive arthritis
Psoriatic arthritis
In which spondyloarthropathy is uveitis predominant?
Ankylosing spondylitis
Reactive arthritis
How does back pain in ankylosing spondylitis present
- Gradual onset of inflammatory back pain > 3 months
- Diffuse and aching
- Worse in morning, including early AM hours - often wake 2nd half night
- Associated stidness
- Not relieved by rest
- Stiffness improves with activity/NSAID
In ankylosing spondylitis, where are the common sites of enthesitis?
- Enthesitis: inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis and joint capsules
- Common sites: achilles tendon, plantar fascia
Clinical signs of long standing ankylosing spondylitis
- Limited spinal mobility
- Limited chest expansion
- Increased neck flexion, increased thoracic kyphosis, decreased lumbar lordosis - stooped posture
Reduced lateral flexion of the lumbar spine is one of the earliest signs of ankylosing spondylitis. There tends to be a loss of lumbar lordosis and an accentuated thoracic kyphosis in patients with ankylosing spondylitis
Difference in mechanisms between psoriatic and RA?
Psoriatic:
- Mechanisms - MHC class 1, no autoantibodies
- Radiological: proliferative, erosive, enthesitis
- Tx: IL17, IL23, TNF inhibitors
RA:
- Mechanisms: MHC class 2, autoantibodies
- Radiological: erosive
- Tx: IL6, TNF inhibitors
Subtypes of psoriatic arthritis
- Distal arthritis (DIP)
- Asymmetric oligoarthritis <5 small and/or large joints
- Symmetric polyarthritis
- Spondylarthropathy including sacroiliitis and spondylitis - in contrast to AS, normally asymmetric and may skip regions
- Arthritis mutilans
More than 1 pattern can occur
Diagnostic criteria of psoriatic arthritis
Established inflammatory articular disease (joint, spine or entheseal) with 3 or more
- Psoriasis (current, historical, family hx in 1st/2nd degree relative)
- Psoriatic nail changes: nail pits, onycholysis, hyperkeratosis, ridging
- RF negative
- Dactylitis - current/historical
- Radiological evidence of juxta-articular new bone formation (hands/feet)
Where is dactylitis a cardinal feature of?
Psoriatic arthritis
What are the nail changes in psoriatic arthritis?
- Nail pits
- Onycholysis: separation of a fingernail or toenail from its pink nail bed
- Hyperkeratosis
- Ridging
Psoriatic arthritis
Arthritis more likely without psoriasis
- Distal joint involvement
- Asymmetric distribution
- Presence of nail lesions (onycholysis) or hidden psoriatic plaques
- Dactylitis
- Family history of psoriasis
Disease associations in psoriatic arthritis?
Obesity Increased cardiovascular risk AMI Hyperlipdaemia/DM/HTN Fatty liver Anxiety/depression Fibromyalgia
Radiological findings of psoriatic arthritis?
Combination of marginal joint erosions and new bone formation - pencil in cup changes
What is the most common cause of mortality in psoriatic arthritis?
Cardiovascular disease
Which hand joints are affected in RA, OA, psoriatic and hemochromatosis?
- RA: symmetrical PIP, MCP with sparing of DIP
- OA: PIP (Bouchard’s), DIP (Heberdens), first carpometacarpal joint
- Psoriatic: DIP and MCP or whole digit (sausage fingers)
- Haemochromatosis: symmetric arthropathy of the MCP joints of digits II and III
Subtypes of IBD associated arthritis
Axial or peripheral
Peripheral joint involvement may be:
- oligoarticular (type 1): acute and remittining OR
- polyarticular (type 2): chronic or frequent relapses
- Only oligoarticular peripheral arthritis parallels IBD activity
Characteristics of type 1 IBD arthropathy
- Affects < 6 joints
- Knees most commonly affected, also ankle MTP
- Often associated with flares
- Self limiting and non-deforming
- Joint symptoms may precede symptoms of bowel disease
Characteristics of type 2 IBD arthropathy
- Polyarticular disease
- MCP joint most frequently involved
- 50% have migatory arthritis
- Acute synovitis may persist for months
- Exacerbations and remissions may continue for years
- Articular involvement rarely precedes diagnosis of IBD
- Joint symptoms do not parallel bowel disease
What bacteria cause reactive arthritis?
- Enteric infections and urethritis
Enteric (she cherishes cooking yummy salmon)
- Shigella (especially flexneri)
- Campylobacter jejuni
- Clostridium difficle
- Yersinia
- Salmonella
Genital: chlamydia trachomatis
Clinical features of reactive arthritis
Classical symptoms
- Diarrhoea or urethritis (discharge +/- dysuria)
- Sexually associated
- Typically 20-30yo
- Onset 1-4 weeks after infection
- Asymmetric oligoarthritis or monoarthritis often affecting the lower limbs (knee/ankle/MTP)
- Dactylitis of toes
- Enthesitis especially achilles, plantar fascia
Reactive arthritis triad (UAC) - Arthritis Asymmetrical, migratory polyarthritis normally affecting knee - Conjunctivitis - Urethritis
Symptoms may include:
- Sacroiliitis
- Enthesis
- Dactylitis
-Skin circinate balanitis (painless vesicles on the coronal margin of the prepuce) keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)
What is reiter’s syndrome
Reactive arthritis
Urethritis
Conjunctivitis
can’t see, can’t pee, can’t climb a tree
In which diseases are the sacroiliac joints affected unilaterally and bilaterally
- Unilateral: psoriatic, reactive
- Bilateral: ankylosing spondylitis, enteropathic
Features of non radiological axial sponduloarthropathy
- Not seen on x-ray but sacroiliitis with inflammation or oedema on non contrast MRI
- Elevated inflammatory markers
- Bone marrow oedema on STIR and T1 images (non contrast)
- Failed NSAIDs and exercise for 3 months
Golimumab (anti tnf) is the only agent on PBS for nr-axSpA
Treatment for psoriatic arthritis
- NSAIDs: symptom relief
- DMRDs: methotrexate, sulfasalazine, leflunomide
- Anti TNF: adalimumab, certolizumab, etanercept, golimumab, infliximab
- Anti-IL17A: secukinumab, Ixekizumab, improve dactylitis and enthesitis
- Anti p40 subunit of IL12/23: ustekinumab, useful for skin>joints, effective for enthesitis/dactylitis
- Anti p19 subunit of IL23: guselkumab
Treatment for reactive arthritis
- Self limited with symptoms resolving within months
- NSAIDs + intra-articular steroid injections
- If progressive/chronic can use dmards such as sulfazalazine, methotrexate, leflunomide
- Abx not normally indicated
Treatment of IBD associated arthritis
- NSAIDs –use with caution
-DMARDs –sulfasalazine, methotrexate; joints and bowel
Not effective in axial disease - Controlling bowel disease often helps
Surgery in Crohn’s not usually helpful - Anti-TNF for joints and bowel except etanercept
- Axial disease treat as per AS –except avoid IL-17 blockers
What medications are effective for axial/spinal disease
- Intra-articular steroids for SI joints
- Steroids: moderate effect
- DMARDS: minimal effect
- Anti-TNF: infliximab, adalimumab, golimumab, certolizumab, etanercept
- IL 17: secukinumab, ixekizumab
What is anti ccp and rf a marker of?
Anti ccp: erosive
RF: extraarticular manifestations
Investigations that need to be done before starting DMARD
CXR Mantoux/quantiferon - if latent TB: 9 months isoniazid or 4 months rifampicin or 12 weeks isoniazid/rifapentin - HBV, HCV, HIV - Strongyloides
What type of TNF inhibitors are: "cept" "mab" "Ximab" "Zumab" "Mumab"
- “cept” fusion of a receptor to the Fc portion of human IgG
- “mab” monoclonal antibody
- “Ximab” chimeric mAb
Chimeric antibodies are structural chimeras made by fusing variable regions from one species like a mouse, with the constant regions from another species such as a human being. - “Zumab” humanized mAb
- “Mumab” fully human mAb
What is RF?
IgM or IgA to Fc portion of human IgG
- Sensitivity 60-80%
- Indicative of extra-articular manifestations, nodules, vasculitis
Also positive in:
- Sjogren
- Cryoglobulinaemia
- SLE
- Dermatomyositis
- Chronic infections - bacterial endocarditis, hep B and C
- Lung diseases (sarcoid, B cell lymphoma)
What is anti CCP
Associated with increased joint damage and low remission rate
Erosions
What are poor prognostic factors of RA?
- Functional limitation
- RF or anti CCP
- Bony erosions documented radiographically
- Smoking
- Extra-articular disease
RF for extra-articular manifestations in RA
Age HLADRB1 Smoking Positive RF or ANA Early disability
Characteristics of gonococcal arthritis (disseminated gonococcal infection)
- Organism: Neisseria gonorrhoea
RF: high sexual activity, unprotected sex, MSM
Clinical Features
1. Arthritis-dermatitis syndrome
- Polyarthralgia: migratory, asymmetrical affecting large and small joints (knees, ankles, wrist, elbow)
- Tenosynovitis: inflammation of several tendons (fingers, toes, wrist, ankle)
- Dermatitis: vesicular, pustular or maculopapular lesions, possibly with a necrotic or haemorrhagic centre
- Fever/Chills
2. Purulent gonococcal arthritis: inflammation of up to 4 joints (commonly knees, wrists, ankles).
No skin manifestations, rarely tenosynovitis.
Tx:
IM/IV ceftriaxone + azithromycin
Cell count for septic arthritis
WCC >50,000
What needs to be checked before azathioprine is given?
Azathioprine - check thiopurine methyltransferase deficiency (TPMT) before treatment Thiopurine methyltransferase (TPMT) deficiency is present in about 1 in 200 people and predisposes to azathioprine related pancytopaenia
Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis. A thiopurine methyltransferase (TPMT) test may be needed to look for individuals prone to azathioprine toxicity.
Adverse effects include bone marrow depression nausea/vomiting pancreatitis increased risk of non-melanoma skin cancer
A significant interaction may occur with allopurinol and hence lower doses of azathioprine should be used.
Azathioprine is generally considered safe to use in pregnancy
Criteria for Biologics in RA
- Methotrexate for 3 months
- A second DMARD for 3 months
Remember: vaccinations prior to biologics if possible, no live vaccines if on biologic
Criteria for Biologics in RA
- Methotrexate for 3 months
- A second DMARD for 3 months
Normal JAK intracellular signalling
- Cytokine binding to its cell surface receptor leads to receptor polymerisation and autophosphorylation of associated JAKs
- Activated JAKs phosphorylate the receptors that dock STATs
- Activated JAKs phosphorylate STATs, which dimerise and move to the nucleus to activate new gene transcription of inflammatory mediators
Tofacitinib, Baracitinib and Upadacitinib compared to methotrexate
Baracitinib and Upadacitinib more effective than combination Mtx + Adalimumab
Surgery and biologics
- Cease 1-2 treatment cycles prior Etanercept 2 weeks Adalimumab 2-4 weeks - Restart when wounds healed - Ritux when B cells normal - Minor surgery no need for cessation
What biologics are recommended for:
- Hep C
- Untreated chronic Hep B
- Treated solid malignancy > 5 years
- Treated solid malignancy < 5 years
- Treated melanoma
- Hep C: entanercept
- Untreated chronic Hep B: no biologic recommended
- Treated solid malignancy > 5 years: any biologic
- Treated solid malignancy < 5 years; Rituximab
- Treated melanoma: rituximab
