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Inflammatory Arthritis in Children
when and why it is important to think rheumatology in the young
Dr Navid Adib
Paediatric Rheumatologist
Queensland Rheumatology Services
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Background: Definitions
• Arthritis
Inflammation at or near a joint
Usually lasting more than just a few days
Chronic arthritis if ≥ 6 weeks (e.g. JIA)
• Synovitis
Synovium is the site of inflammation
There may be fluid accumulation (effusion)
The range of motion (ROM) may be limited
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Background: Definitions
Enthesitis
Inflammation at tendinous or ligamentous insertion near joints or bones
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Inflammation in joints
• Transient synovitis • Unknown frequency
• Usually after URTI
• Boys 2-4x more common
• Mostly described as “irritable hip”, but can happen in any joint
• Lasts 7-10 days
• May recur in some cases; in the same joint or in the contralateral side (hip, knee)
• Some elevation in ESR/CRP
• Immune mediated and not septic arthritis
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Transient synovitis
• Signs and symptoms • Reduced ROM • Pain • disability
• Investigation
• Treatment: rest, control pain (NSAIDs), ?steroid injection if persistent
• Red flags • Septic child (high fevers >38.5°, elevated CRP/ESR ?range) • Non-weight bearing, or ++spasm/++ reduced ROM • Very young age (<1 y.o.) • Not resolving after 2 weeks
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Juvenile Idiopathic Arthritis (JIA)
• Arthritis*, ≥ 6 weeks, <16 y.o., no other cause for arthritis (e.g. IBD, Down S.)
• ILAR classification system • Systemic Arthritis • Oligoarthritis
• Persistent (fewer than 5 joints cumulative count, ≥ 6m) • Extended (5 joints or more, ≥ 6m)
• Polyarthritis RF neg. (5 joints or more, <6m) • Polyarthritis RF pos. (5 joints or more, <6m) • Psoriatic Arthritis (psoriasis, nail dystrophy/pitting, 1st deg relative with pso) • Enthesitis Related Arthritis (male ≥ 6yo, HLA-B27+, 1ST deg relative AS/IBD) • Undifferentiated (unclassifiable)
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Systemic Arthritis
• Probably auto-inflammatory disease (not autoimmune), IL-1, IL-6
• ANA, RF, HLA-B27 usually negative
• Not associated with uveitis
• Characterised by • Usually “sick”, but relatively well between fevers
• Fevers (at least 2 weeks, 3 days quotidian)
• Evanescent rash (?salmon pink)
• Lymphadenopathy, hepatosplenomegaly
• Serositis (ascites, pericardial, pleural effusion)
• Hepatic derangement (LFTs, synthetic function (including coagulopathy)
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Case 1 systemic arthritis
• Female 10yo, Kabuki syndrome
• Fevers, rash
• Joint pains and reduced mobility
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Treatment of systemic arthritis
• Steroids (IV, or oral medium to long course, intra-articular)
• Cytotoxics (methotrexate, cyclosporine A)
• Biologics (IL-1 Anakinra), IL-6 Tocilizumab)
• Cenakinumab
• Sub-cut Tocilizumab
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Oligoarthritis
• High association with ANA (≥1:80)
• Highest association with chronic anterior uveitis (CAU)
• Knee most common presenting joint
• Treatment • IAS
• ?methotrexate (recurrent cases, persistent uveitis)
• ?Biologics (recurrent cases, refractory uveitis)
• Usually best outcome*
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Case 2 Oligoarthritis
• DH, 3yo male
• s/b GP and referred to LCCH, difficult referral and appointment process, long delay before seen
• Not systemically unwell
• Unable to walk, started bum-shuffling
• Seen at the clinic; in wheel chair, unable to weight bear
• Grossly swollen R knee, also both ankles
• Reduced subtalar joint ROM
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Oligoarthritis
• Investigation results
• Arranged intra-articular steroid injections
• Commenced methotrexate treatment
• Referral to physiotherapist
• Referral for uveitis assessment
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Oligo walking video
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Oligo walking video 2
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Oligoarthritis
• Review at the clinic
• No uveitis
• Now can mobilise by walking again
• Pains improved, no gelling or morning stiffness
• Persistence of fixed flexion deformity 15 deg.
• Referred for serial casting
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Oligo walking video 3
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Chronic Anterior Uveitis
• Presence of inflammatory cells in the anterior chamber of the eye
• Painless condition; younger children will not reliably report
• May have photophobia
• Visual acuity affected, not refractory error
• May show injection, irregularity of the pupil
• Advanced cases with glaucoma or cataract
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Band keratopathy
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Uveitis treatment
• Steroid drops (weak to strong types)
• Cycloplegics (Homatropine<atropine)
• Systemic treatment • Oral/IV steroids
• Cytotoxics: methotrexate, cyclosporine
• Biologics: Adalimumab or infliximab
• Intra-ocular • Steroid depot (triamcinolone)
• methotrexate
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Polyarthritis
• Greater number of joints results in • greater disability
• Greater likelihood of chronic inflammation
• More difficult procedure (longer GA, larger steroid dose, cervical spine)
• Less favourable structural outcomes
• Medicare rebated biologic treatment • At least 3 months on methotrexate (20mg/sqm)*
• Concomitant steroid Rx, or hydroxychloroquine/sulfasalazine (“triple therapy”)
• 4 large joints, or 20 large and small joints inflamed simultaneously
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Polyarthritis case
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Psoriatic arthritis
• May have psoriasis, or develop this later
• History of psoriasis, or psoriatic arthritis in first degree relative
• DIPJ involvement
• Onycholysis, nail pitting
• Arthritis mutilans
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Places to look for psoriasis
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Navel
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Severe nail and paronychial inflammation
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Dactylitis, nail dystrophy
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Enthesitis Related Arthritis
• Axial skeleton involvement (SIJs to proximal)
• Large joint involvement (especially hips)
• May have no arthritis (enthesitis only)
• Acute anterior uveitis
• Inherent treatment difficulties • Steroid and methotrexate resistance • SIJs access for steroid injection • ?NSAIDs for spondyitis
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www.qldpaedrheum.com.au
Acute Anterior Uveitis: Hypopyon
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www.qldpaedrheum.com.au
Arthritis In The Context Of Other Diagnoses:
• Inflammatory Bowel Disease Related Arthritis • Often large joints (especially hips)
• Axial skeleton
• Management difficulty
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www.qldpaedrheum.com.au
Arthritis In The Context Of Other Diagnoses:
• Arthritis related to infection • Septic Arthritis
• Staph, Haemophilus, Gonococcal, Tuberculous, Brucella
• Viruses: • Rubella, Parvovirus, Alpha viruses (e.g. Ross River), Mumps, HIV
• Spirochetes (Borrelia burgdorferi in Lyme Disease)
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www.qldpaedrheum.com.au
Arthritis In The Context Of Other Diagnoses:
• Postinfectious arthritis (Arthritogenic bacteria) • Enteric Bacteria: Campylobacter, Salmonella, Shigella, Yersinia
• Chlamydia, Mycoplasma, Giardia, Cryptosporidium
• ?HLA B27 related
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Arthritis In The Context Of Other Diagnoses:
• Reactive arthritis • Reiter’s Syndrome: Arthritis, Conjunctivitis, Urethritis (Gonococcal,
chlamydial).
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Arthritis In The Context Of Other Diagnoses:
• Post Streptococcal Reactive Arthritis
• Rheumatic fever
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www.qldpaedrheum.com.au
Arthritis In The Context Of Other Diagnoses:
• Immune deficiency • congenital immunodeficiency syndromes
• Selective IgA deficiency
• Common Variable Immunodeficiency
• X-Linked Agammaglobulinaemia
Often non-erosive and mild
More often large joints
Mycoplasma infection erosive arthritis
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Arthritis In The Context Of Other Diagnoses:
• Haemoncological disorders • Haemophilia
• Leukaemic joint involvement (chloroma) • ++ pain and disability
• Night pain
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Arthritis In The Context Of Other Diagnoses:
• Connective Tissue Disease (CTD) • Systemic Lupus Erythematosus
• Overlap syndromes (Note RF positive)
• Juvenile Dermatomyositis
• Coexistent with Morphea/Linear Scleroderma
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Arthritis In The Context Of Other Diagnoses:
• Systemic Vasculitides and related syndromes • Henoch Schonlein Purpura
• Kawasaki Disease
• Polyarteritis Nodosa (PAN)
• Relapsing Polychondritis
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www.qldpaedrheum.com.au
Arthritis In The Context Of Other Diagnoses:
Rare syndromes with arthritis
• CINCA (Chronic Infantile Neuro Cutaneous and Articular) Syndrome
• SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) Syndrome
• Recurrent Fever Syndromes • FMF: Familial Mediterranean Syndrome
• HIDS: Hyper IgD Syndrome (Dutch Fever)
• TRAPS: TNF-α Receptor Associated Periodic Fever Syndrome (Familial Hibernian Fever)
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Treatment of arthritis
• Treat to target
• Involve multidisciplinary team: • Physiotherapist
• Occupational therapist
• Nursing support
• Social worker
• Psychologist
• Pharmacist
• Music therapist
• School at hospital
• Biopsychosocial model of care
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Treat to target-Avoid “pyramid” approach
• Completely resolve joint/entheseal inflammation (induction) • Steroid injection/infusion • Rarely oral course
• Simultaneous commencement of appropriate maintenance agent • Methotrexate • Other cytotoxics (Leflunomide, Azathioprine) • Adjuvant medications (Hydroxychloroquine, Sulfasalazine)
• Surveillance • Regular follow up appointments • Blood screening tests (medications, disease activity) • Joint steroid injections • Biologics (to be added on, not replaced with)
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Do NSAIDs work?
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Methotrexate
• Given as low dose (15mg/sqm/wk)
• Oral or subcutaneous (IM hurts!!)
• Slow onset 2-3 months
• Most children tolerate it well
• Others report: • Feeling unwell the day after • May have nausea or vomiting • Rarely mouth ulcers
• Need blood monitoring 1-2 monthly (FBC, ELFTs)
• Safe to handle (pill crusher) if not pregnant
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Steroid injection into joints
• Long acting steroid (Triamcinolone acetonide/hexacetonide)
• Preferably under GA
• May use X-ray guidance or ultrasound
• Usually provides 2-3 months relief (sufficient for mtx to become active)
• Onset usually few days
• Larger joints will require larger dose
• HPA suppression rarely a problem
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Biologics
• Approaches • TNF-α blockers
• IL-6 blockers
• IL-1 blockers
• JAK inhibitors
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TNF-α (cachexin, cachectin)
• Cytokine (cell signalling protein), regulation of immune cells
• Pro-inflammatory molecule via IL-1 and IL-6 signal, pyrogen
• Apoptotic cell death, cachexia
• Inhibit tumorigenesis and viral replication
• Predominantly from activated macrophages, but also • Neutrophils • CD-4 lymphocytes • Natural killer cells • Mast-cells • Eosinophils • Neurons
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Conditions associated with TNF-α
• Alzheimer’s disease, major depression
• Psoriasis, inflammatory bowel disease
• Rheumatoid arthritis, ankylosing spondylitis, JIA
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TNF-α Blockade
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www.qldpaedrheum.com.au
Key Actions Attributed to TNF-a
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Rituximab selectively targets CD20-positive B cells
• B cell depletion occurs via three proposed mechanisms: • Complement-dependent cytotoxicity (CDC)
• Antibody-dependent cellular cytotoxicity (ADCC)
• Apoptosis
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Human microbiome
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Golden Compass?!
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Dust
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Microbiome and arthritis
• Organisms which live on and inside our body
• GI tract dry weight 2kg
• Usually in harmony
• Probably have a role as “gate keepers”
• ?role in conditions such as: • Obesity
• Diabetes
• Arthritis
• Inflammatory bowel disease
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Microbiome
• Child birth
• Antibiotics use
• Diet, ?
• Can they be used for treatment of different conditions
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Take home messages
• NSAIDs are not disease modifying but merely symptomatic treatment
• Using cytotoxics requires familiarity and patient surveillance
• Any child/young person with joint symptoms not resolving after 2 weeks must be referred for evaluation
• If concerned about a case (contracture, significant joint swelling, loss of function)
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