Enthesitis related arthritis & JIA subcategories of ?

David Cabral British Columbia Children’s Hospital Vancouver, CANADA Learning objectives

• ERA /JPsA are they spondyloarthopathies? • How do we classify / diagnose • How are they the same / different • How do we evaluate • How do we treat what is the outcome A Long time ago in a city far, far away …….. Winnipeg 1970s

PATIENT: 12 y Difficulty walking (John) painful swollen knee & painful heel

Diagnosis: Juvenile rheumatoid arthritis Dr Ross Petty ANA - , RF - , HLA-B27+, Enthesitis!

Treatment: naproxen, predisone, Sulphasalazine joint injection, PT, orthotics,

By 17 referred to adult rheumatologist – no arthritis, naproxen only – Occasional Knee + back pain Seronegative Enthesitis & Arthritis

______(SEA) Syndrome

• 39 patients (35 m, 4 f) • Onset 9.8 y (2-16 y) • Enthesitis + arthritis • Negative ANA, RF • Diagnoses – JAS 8 – IBD 2 – 2 – Reiter syndrome 1 – Idiopathic* 26

Rosenberg AM, Petty RE. Arthritis Rheum 25:1041, 1982 ….1990, 10 years later: Vancouver

… Me … … Dr P … ……………

…

Idiopathic SEA syndrome! … … Do boys with a swollen … knee and heel pain end up … … with ? …. 1990, Winnipeg story continues

Back to John (25y) • First rheumatology contact for 5y • Intermittent NSAID use • Increasing back pain attributed to warehouse work & sport • poor fitness, quit football, missing work • Hunched, poor posture, joint , low self esteem → Ankylosing spondylitis first diagnosed! SEA______Syndrome: 10 year outcome

Spondyloarthropathy (SpA) 23 / 26 children ▪ Ankylosing Spondylitis with idiopathic SEA syndrome ▪ Psoriatic Arthritis ______▪ Reiter’s Syndrome spondyloarthropathy 12 ▪ Arthritis of IBD ▪ Undifferentiated SpA • Definite JAS 6 • Possible JAS 5 • Possible PsA 1 • Non-inflammatory disease 5 • JRA (ACR criteria) 4 • Idiopathic SEA syndrome 2 ______

Cabral DA, Oen K, Petty RE. J Rheumatol 19: 1992 Winnipeg was a landmark experience, learn from it you will!

• SEA syndrome patients likely develop AS. • Window of improvement before relapse. • Prognostication and close follow-up especially through transition period is important • Relapse / onset of back disease may be insidious • SEA syndrome became ERA ERA = enthesitis related arthritis Enthesitis related arthritis ______Arthritis and enthesitis or Arthritis or Enthesitis, and 2 of • SI joint tenderness +/or back pain • HLA-B27 • FH (10) HLA-B27 disease • Acute anterior • Onset in boy over 6

and do not have: Psoriasis; FH of psoriasis; RF; systemic symptoms Juvenile Idiopathic Arthritis (JIA): subset %

ILAR Classification of JIA SA Can Ind W.Eur • Systemic arthritis 8 6 8 16 • Oligoarthritis - persistent 27 43 21 51 - extended • Polyarthritis (RF +) 14 3 12 32 • Polyarthritis (RF - ) 27 18 17 • Psoriatic arthritis 1 7 1 ? • Enthesitis related arthritis 23 14 36 ? • Unclassified ? 10 5 ?

• Weakly, Esser, Scott, Ped Rheumatol 2012 • Guzman, Oen et al Annals Rheum.Dis 2016 Juvenile Idiopathic Arthritis (JIA): subsets

ILAR Classification of JIA Adult equivalents • Systemic arthritis AInD • Oligoarthritis - persistent - extended RA-like • Polyarthritis (RF +) • Polyarthritis (RF - ) • Psoriatic arthritis ?? • Enthesitis related arthritis SpA-like Unclassified Juvenile Idiopathic Arthritis (JIA): subsets

ILAR Classification of JIA Adult equivalents • Systemic arthritis AInD • Oligoarthritis - persistent - extended RA-like • Polyarthritis (RF +) • Polyarthritis (RF - ) • Psoriatic arthritis ?? • Enthesitis related arthritis SpA-like Juvenile ankylosing spondylitis Unclassified Juvenile Psoriatic arthritis (JPsA) ______

Arthritis and Psoriasis or Arthritis and >2 of • dactylitis • nail pitting or onycholysis • FH (10) of psoriasis

and do not have: HLA B-27 boy>6; systemic symptoms RF; FH of HLA-B27 disease, JPsA Characteristics ______• Age at onset: Bimodal peaks • Sex ratio: 1:1.6 (M:F) • Joint involvement: typically asymmetric small and large joints pattern: oligoarticular -> polyarticular; dactylitis characteristic • Sacroiliac joint changes: <10 % • Enthesitis: <10 % • Chronic anterior uveitis: 15 % • RF: absent; ANA: 30 – 60 %

Huemer C, Malleson PN, Cabral DA, et al: J Rheumatol 29:1531, 2002 JPsA: Diagnosis obvious! …….. but not always! ______

• Diagnosis may not be considered • Psoriasis not present, or not looked for.. • Psoriasis may be difficult to diagnose • Nail pitting is frequently transitory • The characteristic pattern of joint involvement may not be noted. • Reliable family histories are difficult JPsA a spondyloarthropathy?

Adult JPsA phenotypes • Asymmetric oligoarthritis* • Symmetric RA-like arthritis* Only 40% develop • Predominant DIP joint arthritis • sacroiliitis • spondylitis Questions about Psoriatic Arthritis ______

oligo/polyarthritis or spondyloarthropathy Is presence of psoriasis simply coincidental and a modifying influence?

Similar questions can apply to IBD-associated arthritis Juvenile Idiopathic Arthritis (JIA)

Other Classification of JIA Systemic arthritis AInD Qualifiers Idiopathic Peripheral • Oligoarthritis arthritis • • Polyarthritis ANA (no axial disease) • RF • HLA-B27 • Other Idiopathic • ERA …….biomarkers Spondyloarthropathy • JAS (+/- peripheral ) • Psoriasis • IBD Unclassified arthritis ? Evaluating JSpA

.. & some pearls and myths ______Evaluating JSpA

Usually no inflammatory back pain or sacroiliitis but presents as undifferentiated disease: i.e. ERA

Enthesitis a critical defining feature of ERA Enthesitis difficult to evaluate: DD? ______

Mechanical / structural / Muscle imbalance • Flat feet • poor fitting shoes? • repetitive stress • patello-femoral / iliotibial band Osteochondroses • Severs, Osgood-Schlatter’s , iselins, Sinding-Larssen- Johansen’s etc Pain syndromes CRMO Evaluate (ERA) in context ______

• HLA-B27 +/or FH of SpA • arthritis • Transient • single site • Tender at non- entheseal sites • imaging Enthesitis vs CRMO

7-yr-old girl: proximal tibia pain

9-yr-old boy: heel pain

5-yr-old boy: knee pain Peripheral Arthritis Characteristics ______Asymmetric, lower limb oligoarthritis common • Hips • Knees • Ankles Uncommon • Mid foot (characteristic) Examining for mid-foot disease Evaluating axial disease

Arthritis and enthesitis or Arthritis or Enthesitis, and 2 of •SI joint tenderness +/or back pain •HLA-B27 •FH (10) HLA-B27 disease •Acute anterior uveitis •Onset in boy over 6 Evaluating Back pain Pre Adolescents Puberty Localised + Discitis + Osteomyelitis + + Tumor + Spondylo –lysis /-listhesis + Scheuermann’s disease + + CRMO + Diffuse malignancy + structural / ergonomic + pain amplification + +/- inflammatory back pain + 4-yr-old with back pain. 15 yr-old mid-thoracic sclerosis L3 vertebra back pain Low Back pain 15 yr-old Axial Arthritis in kids: Clinical Characteristics ______

• Often asymptomatic • Buttock pain (more likely ischial tuberosity enthesitis) • Localized morning Stiffness • Tenderness over SI Joints, LS-Spine, (? C-Spine) • Clinical manoevres …. Clinical manoevres Reduced back range Schober’s measurement Flattening

FABER test

Mennel’s sign

Caution diagnosing sacroiliitis without arthritis imaging normal sclerosis Bilateral erosions & joint space widening 7-year-old boy with back pain. 16 year old with low back /SI pain When to do MRI?

• To diagnose sacroiliitis (radiographs normal)

• To exclude sacroiliitis • To track disease activity Treatment … a cascade of drugs

• NSAIDS • peripheral arthritis • enthesitis – naproxen, ibuprofen, et al • Sacroiliitis • corticosteroid May need to be targeted differently – Intra-articular – Low dose oral • DMARDs – methotrexate, sulphasulazine, • Biologic agents – Anti-TNF …outcomes Inactive disease within 2 years Remission within 5 years Flare one year after inactive

Oligoarthritis

Polyarthritis RF-Neg

Enthesitis-related

Psoriatic

Systemic

Polyarthritis RF-Pos

Undifferentiated

.

0 20 40 60 80 100

Guzman J, Oen K, et al Ann Rheum Dis 2016;75:1092-8. Flare one year after treatment stop JIA outcomes with & without enthesitis Overview

• ERA (SpA) the most difficult category of JIA to diagnose

• Distinguishing inflammatory vs non- inflammatory disease is an imperative

• The morbidity & poor outcome associated with enthesitis is under appreciated

• Earlier more aggressive treatment may help