Axial Spondyloarthropathy Dr Rosh Sathananthan FRCP Consultant Rheumatologist

Case 1: Age 40 year old man Long standing history of back pain since a teenager Neck, lower back and buttock area Early morning stiffness 2 hours Symptoms severe until excluding meat and dairy from diet Medication: Ibuprofen 200mg bd

Last episode 12 months ago Past medical history: Psoriasis Recurrent uveitis Last episode 12 months ago Suggested by ophthalmologists he may have Axial SpA HLA B27 positive Blood tests: ESR 29 CRP 14

Examination Restricted ROM cervical, thoracic and lumbar spine Chest expansion 4.5 cm Schober’s index 5 cm Hip movements normal

MRI Scan: Thoracic spine: Lumbar spine: Sacroiliac joints: Fusion of the posterior elements T1-6 Inflammation costovertebral and uncovertebral joints Lumbar spine: No significant inflammatory changes Sacroiliac joints: Almost complete fusion but no bony oedema

Case 1 BASDAI 6.7 Spinal VAS 6 Not keen on biologics at present or increased dose of NSAID Jointly agreed tracking of BASDAI and further review Recommended NASS group at CUH – prefers self management

Case 2 Age 38 year old man Nine years low back pain, buttocks and back of legs Early morning stiffness of 30 mins Naproxen extremely effective in controlling pain Recurrent uveitis – currently quiescent No psoriasis No family history of spondyloarthropathy

Examination: Restricted ROM cervical, thoracic and lumbar spine Reduced neck flexion. Tender lower thoracic spine Reduced chest expansion 4 cm Schober’s index 3 cm Hip examination normal HLA B27 positive ESR 23 CRP 26

MRI Scan: Thoracic spine: Lumbar spine: Sacroiliac joints: Corner lesions T 1-2, T 4-5, T 9-11 Florid changes costotransverse joints T 8-9 Lumbar spine: Corner lesions L2/3 and L4/5 Inflammatory changes facet joints right L4/5 and L5/S1 Sacroiliac joints: Oedema at the lateral inferior sacral margins

Case 2 High BASDAI score No improvement with NSAIDs Treated with TNF inhibitor – etanercept Has been attending NASS group at CUH

Case 3 Age 53 year old man Over 10 year history of low back pain Episodic flares Early morning stiffness over 60 minutes History of Crohn’s disease (stable) Chronic bilateral uveitis No psoriasis or family history of spondyloarthropathy

Examination Generalised lumbar tenderness but good ROM Schober’s index 8 cm Chest expansion 3 cm HLA B27 negative ESR 5 CRP 12 BASDAI 6.0 Spinal VAS 6.0

MRI spine Cervical spine: Thoracic spine: Sacroiliac joints: Normal Vertebral corner lesions at several levels Costovertebral oedema at T8 Sacroiliac joints: Small amount of oedema at the sacroiliac joint margin bilaterally

Management Current BASDAI 4.9 Ibuprofen PRN Colitis stable for 10 years Suggested regular NSAID - etoricoxib Referred to physiotherapy

Case 4 Age 29 year old man Psoriasis 2 years Joint pains for 12 months increasing in severity Wrists, elbows, shoulders, hips, knees, ankles – mild MCPJ TMJ – unable to fully open mouth Severe neck pain No IBD symptoms. No history of uveitis

Examination Unwell and pale Profuse sweating Stiff neck with very limited extension/lateral rotation Reduced EOR thoracic rotational movement Good ROM lumbar spine Restricted painful hips, shoulders and wrists Swollen elbows unable to straighten History of tick bite a few months earlier (Lyme serology negative)

Investigations ESR 18 CRP 100 HLA B27 negative MRI scan: Oedema right costovertebral joint Increased oedema around the inferior margins of SIJ bilaterally Bilateral florid synovitis of both hips with effusions BASDAI 6.7 Spinal VAS 7/10 Diagnosis: Psoriatic spondyloarthopathy with peripheral arthritis

Treatment Ibuprofen switched to Naproxen – no improvement Prednisolone Methotrexate – no improvement TB screening Currently on etanercept: BASDAI 2.8 ESR 2 CRP < 1.0

Spondyloarthropathy Axial Spondyloarthritis (Ax-SpA) Psoriatic arthritis Reactive arthritis (related to HLA B27) Enteropathic arthritis (Crohn’s/Ulcerative colitis JIA ( Enthesitis-related /Psoriatic-related)

Axial Spondyloarthritis Non-radiographic Axial-SpA (nr-axSpA) Ankylosing Spondylitis Active inflammation on MRI suggestive of sacroiliitis + Other findings Radiographic (X-ray) changes of sacroiliitis modified New York criteria

Axial Spondyloarthritis 50% of non-radiographic axial-SpA (nr-axSpA) are women 5-12% of nr-axSpA will develop radiographic change over 2 years 15-20% will never develop radiographic sacroiliitis Predictors of progression to AS: Male HLA B27 +ve Raised inflammatory markers Significant inflammation on MRI (bone marrow oedema) Smoking

Spondyloarthritis: Facts and figures: Spondyloarthritis: Facts and figures: State of Musculoskeletal Health 2018 Prevalence 1/200 Average age onset of symptoms 24 years Age < 45 at disease onset 90-95% Average delay to diagnosis 8.5 Inflammatory back pain symptoms 89% of nr-axSpA/AS patients Depression 10% (doctor diagnosed) Loss of employment 5% (1 year) 20% (10 years) 30% (20 years)

ASAS criteria for identifying inflammatory back pain ASAS criteria for identifying inflammatory back pain Sieper J et al Ann Rheum Dis 2009;68(6):784-8 Back pain for more than 3 months: Did your back pain start when you were age 40 years or under? YES/NO Did your back pain develop gradually? Does your back pain improve with exercise? Do you find there is no improvement in your back pain when you rest? Do you suffer from back pain at night which improves on getting up? Yes to 4 or more parameters suggest inflammatory back pain 77% sensitive 91.7% specific and warrants further investigation

Other symptoms of inflammatory back pain Good response to NSAIDs Early morning Stiffness greater than 30 mins Alternating buttock pain Waking in the second half of the night with back pain

Extra articular manifestations Enthesitis Any entheses Lower limb: Achilles and or plantar fasciitis 14% Ankylosing spondylitis 20% Non-radiographic AxSpA Uveitis Most common 20-30% Risk throughout the course of disease. Crohn’s/UC 5-10% of patients Dactylitis 5-6% Psoriasis 9% Plaque psoriasis/nail dystrophy Often present before diagnosis of Ax-SpA

HLA B27 HLA B27 is a susceptibility gene Prognostic feature of axial-SpA HLA B27 positive General population 8-9% Ankylosing spondylitis up to 95% HLA B27 negative does NOT rule out axial SpA

HLA B27 and spondyloarthritis Reveille J Clinical immunology(3rd edition) 2008 HLA B27 prevalence Ankylosing spondylitis Up to 95% Reactive arthritis 70% Inflammatory bowel disease 50-60% Psoriatic Spondyloarthritis 60-70% Psoriatic arthritis 25% Acute anterior uveitis 50%

Diagnosis No formal diagnostic criteria exist for axial SpA ASAS Classification Criteria can guide clinical assessment and diagnosis Other causes of back pain need to be excluded Look out for ‘Red Flags’ Diagnosis of axial SpA is made by a combination of clinical features, imaging and blood tests Negative HLA B27 does not rule out axial SpA Inflammatory markers may be normal

In patients with ≥ 3 months and age at onset < 45 years ASAS classification criteria for Axial SpA Rudwaleit Met al Ann Rheum Dis 2009;68(6):777-783 In patients with ≥ 3 months and age at onset < 45 years Sacroiliitis on imaging + ≥ 1 SpA feature HLA B27 positive ≥ 2 other SpA features

Sacroiliitis on imaging ASAS classification criteria for Axial SpA Rudwaleit Met al Ann Rheum Dis 2009;68(6):777-783 Sacroiliitis on imaging Active inflammation on MRI suggestive of sacroiliitis Radiographic (X-ray) changes of sacroiliitis modified NY criteria

SpA features Inflammatory back pain Arthritis Heel enthesitis Uveitis Dactylitis Psoriasis Crohn’s disease/Ulcerative colitis Good response to NSAIDs Family history of SpA HLA B27 positive Elevated C-reactive protein Other causes of back pain have been ruled out

Management Patient education on SpA Lifestyle, smoking, flare management Clinical outcome measures BASDAI/Spinal pain score Physiotherapy/Exercise Manage comorbidities Cardiovascular disease, diabetes, osteoporosis Depression, pulmonary function Treatment according to NICE guidelines NSAIDs/Biologics

TREATMENT Control of symptoms and inflammation Prevention of progressive structural damage. Preserve or normalise function Monitor for extra-articular manifestations (EAMS) EAMS should be considered when choosing treatment Standard therapy: 2 NSAIDs for at least 2 weeks unless contraindicated Biologics criteria: BASDAI and spinal VAS ≥ 4 in spite of standard therapy

BIOLOGIC DMARDS TNF inhibitors Radiographic and nr-axial SpA IL-17 inhibitor Radiographic axial SpA Adalimumab Seckukinumab Certolizumab pegol Golimumab Infliximab Etanercept (fusion protein)

SUMMARY Spondyloarthritis is characterised by a broad spectrum of disorders associated with HLA B27 Inflammatory back pain is a hallmark symptom of axial-SpA 50% of non-radiographic-SpA are women Radiographic and non-radiographic axial-SpA have a similar clinical picture Extra articular manifestations are often associated with axial-SpA Negative HLA B27 and normal inflammatory markers do not exclude spondyloarthropathy High index of suspicion and prompt referral to secondary care is important for early diagnosis, management and to improve outcomes