Spondyloarthropathies — DCE Clinical Case

Long Case — Ankylosing spondylitis with extra-articular manifestations

Patient scenario

Mr Robert Thompson is a 48-year-old electrician presenting to the physician clinic for review of his long-standing ankylosing spondylitis and several new symptoms. [1]

History of presenting complaint: [1]

• Twenty-two years ago: diagnosed with ankylosing spondylitis at age 26 after 3 years of inflammatory back pain (insidious onset, morning stiffness, improvement with exercise, night pain). HLA-B27 positive. Pelvic radiograph showed bilateral grade 3 sacroiliitis. Initially managed with NSAIDs (diclofenac, then naproxen) and physiotherapy with moderate control.
• Fifteen years ago: developed acute anterior uveitis (left eye) — resolved with topical corticosteroids. Has had four further episodes since (three left, one right), the most recent 6 months ago.
• Ten years ago: started adalimumab 40 mg subcutaneously every 2 weeks after inadequate response to two NSAIDs and significant functional limitation. Good initial response — BASDAI dropped from 7.1 to 3.2.
• Five years ago: noted new exertional dyspnoea and reduced exercise tolerance. Echocardiogram showed mild aortic regurgitation (aortic root dilation from aortitis). No conduction disease on ECG.
• Three months ago: routine chest X-ray showed bilateral upper-zone reticulonodular changes; HRCT confirmed apical pulmonary fibrosis with pleural thickening.
• Now: increasing back stiffness, BASDAI 5.8, ASDAS-CRP 3.2 (high disease activity) despite adalimumab. He is struggling to work and has reduced his hours. [1]

Past medical history: Ankylosing spondylitis (22 years). Osteoporosis (diagnosed 5 years ago on DEXA — T-score minus 2.8 at the lumbar spine). Acute anterior uveitis (multiple episodes). Mild aortic regurgitation. Apical pulmonary fibrosis. Hypertension (5 years, on ramipril). Former smoker (20 per day for 20 years, quit 8 years ago). [1]

Medications: Adalimumab 40 mg subcutaneously every 2 weeks. Naproxen 500 mg twice daily. Alendronate 70 mg weekly with calcium and vitamin D. Ramipril 10 mg daily. Pantoprazole 20 mg daily. [1]

Family history: Father with ankylosing spondylitis. Sister with psoriasis. [1]

Social history: Electrician. Married. Former smoker (20 per day for 20 years, quit 8 years ago). Occasional alcohol. Two adult children. [1]

Examination findings: [1]

• Afebrile, heart rate 76, blood pressure 138/84, respiratory rate 18, oxygen saturation 96 per cent on room air.
• Spine: Loss of lumbar lordosis, increased thoracic kyphosis, forward neck posture (question-mark posture). Occiput-to-wall distance 8 cm. Modified Schober expansion 2 cm. Chest expansion 1.5 cm at the fourth intercostal space. Cervical rotation 30 degrees bilaterally.
• Enthesitis: Tenderness at both Achilles tendon insertions.
• Cardiac: Early diastolic murmur at the left sternal edge (aortic regurgitation). No gallop.
• Respiratory: Fine inspiratory crackles at both apices. Reduced chest expansion.
• Eyes: No active uveitis. Old synechiae visible on the left.
• Abdomen: Unremarkable.
• Neurological: No focal deficit. Normal power, tone and reflexes in all four limbs. [1]

Investigations: [1]

Candidate's opening statement (model answer — SASPOP format)

"Mr Robert Thompson is a 48-year-old electrician with a 22-year history of HLA-B27 positive ankylosing spondylitis, currently on adalimumab and naproxen with inadequate disease control (BASDAI 5.8, ASDAS-CRP 3.2 — high disease activity), who presents with multiple significant problems reflecting advanced multisystem disease. [1]

His main problems are:

1. Ankylosing spondylitis with secondary loss of biologic response — ASDAS 3.2 despite adalimumab for 10 years, with a bamboo spine, reduced spinal mobility (occiput-to-wall 8 cm, modified Schober 2 cm, chest expansion 1.5 cm), and active inflammation (CRP 34).
2. Recurrent acute anterior uveitis — five episodes, most recent 6 months ago; cumulative synechiae risk; his drug choice must address this.
3. Cardiovascular — mild aortic regurgitation from aortitis (stable on echo) and a coronary risk equivalent from chronic inflammation and his smoking history.
4. Respiratory — apical pulmonary fibrosis with pleural thickening and traction bronchiectasis; restrictive pattern on spirometry (FVC 72 per cent, DLCO 64 per cent).
5. Bone health — osteoporosis (T-score minus 2.9) with a fused brittle spine and high fracture risk.
6. Occupational impact — reduced working hours, threatened livelihood. [1]

My immediate priorities are: first, address the loss of biologic response — switch adalimumab to an alternative biologic (secukinumab, an IL-17 inhibitor, or switch TNFi class); second, cardiovascular and respiratory assessment and management; third, fracture risk management; fourth, uveitis prevention. The uveitis history is a key determinant of drug choice — adalimumab should be preventing it, so his recurrent episodes despite adalimumab suggest either secondary loss of efficacy or an alternative mechanism." [1]

Integrated management plan

1. Loss of biologic response — biologic switch (the immediate priority): [1]

• His ASDAS-CRP is 3.2 (high disease activity) despite 10 years of adalimumab. Under the ASAS-EULAR 2022 recommendations [4], this warrants a biologic switch. Options:

  • Switch to another TNFi — try a different TNFi (e.g., golimumab 50 mg monthly, or certolizumab 400 mg then 200 mg every 2 weeks). Approximately 40 to 50 per cent of patients who fail one TNFi respond to a second. However, given he has been on adalimumab for 10 years, secondary loss of efficacy (anti-drug antibodies, disease progression) is likely.
  • Switch to an IL-17 inhibitor — secukinumab 150 mg subcutaneously weekly for 4 weeks then monthly, or ixekizumab 80 mg every 2 weeks then monthly. The MEASURE 1 trial showed ASAS20 response in 60 per cent at week 16 [3]. An IL-17i is a rational choice because it targets a different cytokine pathway (IL-17 rather than TNF), and has good efficacy for both axial disease and psoriasis (relevant given his sister has psoriasis). However, the uveitis concern applies — IL-17i have a modest but not strong uveitis-reducing effect.
  • Switch to a JAK inhibitor — tofacitinib 5 mg twice daily or upadacitinib 15 mg daily. The Deodhar phase 3 trial showed tofacitinib ASAS20 in 56 per cent versus 29 per cent placebo [6]. However, he is 48 (approaching the over-50 threshold) with hypertension and a smoking history — cardiovascular caution applies (ORAL Surveillance data from RA).

• My choice: I would switch to secukinumab (IL-17i). He has failed one TNFi mechanism after 10 years. IL-17i targets the IL-23/IL-17 axis central to SpA pathogenesis. The uveitis concern is real but secukinumab does have a modest uveitis-reducing effect, and his recurrent uveitis despite adalimumab suggests the TNF pathway alone is insufficient for his uveitis. I would screen for latent TB (IGRA) and HBV/HCV before switching (he should have ongoing surveillance already), and counsel on the IBD risk (he has no IBD, so IL-17i is safe from that perspective). [1]

2. Acute anterior uveitis: [1]

• He has had five episodes despite adalimumab. The recurrent uveitis despite TNFi suggests either inadequate TNFi levels (anti-drug antibodies) or an IL-17-driven uveitis mechanism. The switch to secukinumab may or may not help — IL-17i has a less robust uveitis-preventing effect than monoclonal TNFi. I would maintain close ophthalmology surveillance (slit-lamp every 6 months even when asymptomatic) and counsel on early symptom recognition. [1]

3. Aortic regurgitation: [1]

• His AR is mild and stable (aortic root 38 mm, stable on serial echo). Management: annual echocardiogram to monitor progression, afterload reduction with ramipril (already on it), and surgical referral if he develops symptoms or significant LV dilation. No change needed at present. [1]

4. Apical pulmonary fibrosis: [1]

• The apical fibrosis is a recognised complication of long-standing AS (pleuropulmonary inflammation analogous to the spinal enthesitis). Management: refer to a respiratory physician for shared care. Serial PFTs (FVC, DLCO) every 6 to 12 months. Consider an antifibrotic (nintedanib) if there is progressive fibrosing disease (based on the INBUILD trial for progressive fibrosing ILD). Stop smoking (already quit). Monitor oxygen saturations. [1]

5. Osteoporosis and fracture risk: [1]

• He has osteoporosis (T-score minus 2.9) with a fused, brittle bamboo spine. Management: continue alendronate, calcium and vitamin D. Consider switching to denosumab or an anabolic agent (teriparatide) if fracture risk is very high. Annual DEXA with vertebral fracture assessment. Most importantly, counsel on the fracture risk — the bamboo spine is fragile; any fall needs full spine imaging. As an electrician who may work at heights, occupational safety is critical. [1]

6. Cardiovascular risk: [1]

• AS is a coronary risk equivalent (chronic inflammation accelerates atherosclerosis). He is a former smoker with hypertension. Management: calculate cardiovascular risk, optimise blood pressure (already on ramipril — target 130/80 or below), check a fasting lipid panel and start a statin if indicated, encourage regular exercise (adapted for his spine), and minimise NSAID exposure (NSAIDs raise blood pressure and cardiovascular risk). [1]

Communication and shared decision-making

I would sit with Mr Thompson and his wife in a private room. My key messages: [1]

• "Your ankylosing spondylitis has been well controlled on adalimumab for 10 years, but it is no longer working as effectively as it was. The inflammation markers are up and your symptoms are worse. I think we need to switch to a different medication — one that targets a different part of the immune system. This is called secukinumab, and it blocks a protein called IL-17. It works well for the spine and for the skin problems that run in your family. We will need to do the same screening tests we did before starting adalimumab — checking for old tuberculosis infections and hepatitis." [1]

• "Your eye inflammation (uveitis) is a concern. Adalimumab usually prevents this, but you have still had episodes. The new medication may help, but we will need to watch closely. If you get a painful red eye, you need to see an eye doctor the same day — do not wait." [1]

• "Your spine has become quite stiff over the years — this is why we see the bamboo-like appearance on the X-ray. The stiffness means the spine is more fragile, like a stick rather than a flexible column. This is important: if you fall, even if it seems minor, you must go to the hospital and tell them you have ankylosing spondylitis and need a CT scan of your spine. Even if the pain seems manageable, a fracture could be serious." [1]

I would document the shared decision, provide written information, and arrange a named clinical contact. [1]

Probing questions and model answers

Examiner: How do you approach the loss of response to adalimumab, and what is your drug sequence? [1]

"Loss of response to a TNF inhibitor is common — it can be primary (no initial response) or secondary (initial response followed by loss of efficacy, often from anti-drug antibodies). For Mr Thompson, this is secondary loss of response after 10 years. [1]

My drug sequence under the ASAS-EULAR 2022 recommendations [4]: first, confirm active disease with ASDAS-CRP (3.2 — high disease activity confirmed). Second, ensure adherence and check for anti-drug antibodies and trough adalimumab levels if available — low trough levels with high antibody titres confirm immunogenicity-driven loss of efficacy. Third, switch the biologic — either to another TNFi (golimumab, certolizumab) or to a different class (IL-17i: secukinumab, ixekizumab; or JAKi: tofacitinib, upadacitinib).

For this patient, I prefer switching to secukinumab (IL-17i) because it targets the IL-23/IL-17 axis central to SpA pathogenesis. The MEASURE 1 trial showed robust ASAS20 response [3]. If secukinumab fails, my next step would be a JAK inhibitor — tofacitinib showed ASAS20 in 56 per cent versus 29 per cent placebo in the phase 3 trial [6] — with the cardiovascular caution noted given his age and risk factors."

Examiner: What is the significance of the apical pulmonary fibrosis, and how does it differ from the interstitial lung disease of rheumatoid arthritis? [1]

"Apical pulmonary fibrosis is a well-recognised but relatively uncommon complication of long-standing ankylosing spondylitis, occurring in 1 to 2 per cent of patients. It is distinct from the ILD of rheumatoid arthritis in several ways: it preferentially affects the upper lobes (RA-ILD is basal-predominant UIP), it involves pleural thickening and sometimes cavitation (mimicking TB), and the mechanism is pleuropulmonary inflammation analogous to the enthesitis of the axial skeleton rather than the autoimmune pneumonitis of RA. [1]

For Mr Thompson, the HRCT shows bilateral apical fibrosis with pleural thickening and traction bronchiectasis — a fibrotic, progressive pattern. Management involves shared care with a respiratory physician, serial PFTs (FVC, DLCO) every 6 to 12 months, and consideration of an antifibrotic (nintedanib) if there is progressive fibrosing disease. The restrictive pattern on spirometry (FVC 72 per cent) and reduced DLCO (64 per cent) are consistent with significant but not yet severe disease." [1]

Examiner: Why is he still getting uveitis on adalimumab? [1]

"Adalimumab is proven to reduce uveitis recurrence in AS — it is one of the reasons monoclonal TNFi are preferred over etanercept for patients with uveitis. However, no drug completely prevents uveitis. Several explanations for his continued episodes: [1]

First, secondary loss of efficacy — the same anti-drug antibodies that reduce his spinal response may also reduce his uveitis protection. Checking trough adalimumab levels and anti-drug antibodies would help confirm this. Second, his uveitis may be partially driven by pathways other than TNF — IL-17 or IL-23 pathways may contribute, and the switch to an IL-17i may or may not help. Third, the recurrent nature of AS-associated uveitis means that even with optimal therapy, breakthrough episodes occur. [1]

My approach: check adalimumab trough levels and anti-drug antibodies to confirm immunogenicity. Switch to secukinumab, which may provide better overall disease control even if the uveitis benefit is uncertain. Maintain close ophthalmology surveillance — slit-lamp every 6 months even when asymptomatic, because subclinical inflammation can cause cumulative damage." [1]

Examiner: What is his fracture risk and how do you manage it? [1]

"His fracture risk is very high. He has three compounding factors: osteoporosis (T-score minus 2.9), a rigid fused spine that concentrates mechanical forces, and the chronic inflammatory state that promotes osteoclast activation. The bamboo spine behaves like a long bone — a minor fall can cause an unstable three-column fracture at the cervicothoracic or thoracolumbar junction, with a high rate of neurological deficit. [1]

Management: first, continue alendronate, calcium and vitamin D. Consider upgrading bone protection — denosumab 60 mg subcutaneously every 6 months is an alternative, or an anabolic agent (teriparatide or romosozumab) if fracture risk is very high and he has not yet had a vertebral fracture. Second, annual DEXA with vertebral fracture assessment (VFA) — standard DEXA may underestimate risk in the fused spine because the syndesmophytes artificially elevate the bone density reading. Third, and most importantly, safety counselling — the patient must understand that any fall, even a low-energy fall from standing, requires full spine imaging (CT then MRI if needed). As an electrician who may work at heights, occupational safety assessment is warranted." [1]

Short Case — Spine examination: ankylosing spondylitis

Examination instruction

"Examine this patient's spine. He is a 48-year-old man with chronic back pain." [1]

Systematic examination routine

Step 1 — Inspect at the end of the bed:

• General appearance — the patient stands with a characteristic forward-flexed posture.
• Look for the question-mark posture: loss of lumbar lordosis, increased thoracic kyphosis, forward neck.
• Walking aids, shoe raises, functional limitation. [1]

Step 2 — Inspect the spine:

• Examine from behind and from the side.
• Loss of lumbar lordosis (flat lower back).
• Increased thoracic kyphosis.
• Reduced cervical extension (forward chin).
• No surgical scars. [1]

Step 3 — Palpate:

• Palpate the spinous processes for tenderness and step deformity.
• Palpate the sacroiliac joints for tenderness (direct pressure or sacroiliac compression).
• Palpate the Achilles tendon insertions and plantar fascia origins for enthesitis (heel tenderness is a key SpA sign). [1]

Step 4 — Assess spinal movement:

• Occiput-to-wall distance: patient stands with heels and back against the wall; measure the distance from the occiput to the wall. Normal: 0 cm. Above 0 cm is abnormal (reduced cervical and upper thoracic extension).
• Modified Schober test: mark 10 cm above and 5 cm below the line connecting the posterior superior iliac spines. Measure the increase on maximal forward flexion. Normal: above 5 cm. Below 5 cm is abnormal.
• Cervical rotation: assess bilaterally. Normal: above 70 degrees.
• Lateral flexion: slide the hand down the lateral thigh. Measure the difference. Reduced in AS. [1]

Step 5 — Assess chest expansion:

• Measure at the fourth intercostal space, arms abducted. Normal: above 2.5 cm (optimally above 5 cm). Below 2.5 cm is abnormal (reduced costovertebral joint mobility). [1]

Step 6 — Screen for extra-articular manifestations:

• Eyes: signs of previous uveitis (synechiae, irregular pupil).
• Heart: aortic regurgitation murmur (early diastolic at the left sternal edge).
• Chest: apical crackles (pulmonary fibrosis).
• Skin and nails: psoriasis, nail pitting (if co-existing psoriatic features). [1]

Presentation template

"This patient has the classical posture and signs of advanced ankylosing spondylitis. On inspection, there is loss of lumbar lordosis, increased thoracic kyphosis, and a forward neck — the question-mark posture. The occiput-to-wall distance is 8 cm (normal 0 cm), confirming reduced cervical and upper thoracic extension. The modified Schober expansion is 2 cm (normal above 5 cm), confirming reduced lumbar flexion. Chest expansion is 1.5 cm (normal above 2.5 cm), indicating reduced costovertebral joint mobility. Cervical rotation is reduced to 30 degrees bilaterally. There is tenderness at both Achilles tendon insertions, consistent with enthesitis. [1]

These findings, with the reduced spinal mobility in all planes and enthesitis, are consistent with advanced ankylosing spondylitis. I would like to complete my examination by screening for extra-articular manifestations: examining the eyes for signs of previous uveitis, the heart for aortic regurgitation, the chest for apical pulmonary fibrosis, and the skin for psoriasis."* [1]

Discussion questions

Examiner: "What is the significance of the reduced chest expansion?" [1]

"Reduced chest expansion below 2.5 cm at the fourth intercostal space is one of the modified New York clinical criteria for ankylosing spondylitis [1]. It reflects involvement of the costovertebral and costotransverse joints — the same inflammatory enthesitis process that affects the sacroiliac and spinal joints. Over years, these joints fuse, restricting rib movement and forcing the patient to rely increasingly on diaphragmatic breathing. This has two consequences: first, functional limitation (reduced exercise capacity, which this patient reports); second, restrictive lung disease (his FVC of 72 per cent predicted is partly due to reduced chest wall compliance, partly due to the apical fibrosis).

The reduced chest expansion is an objective, reproducible measure of disease severity that can be monitored over time — it worsens with disease progression and improves with effective treatment and physiotherapy."* [1]

Examiner: "How would you differentiate this from diffuse idiopathic skeletal hyperostosis (DISH)?" [1]

"DISH (Forestier disease) is a differential for spinal ossification in older patients. The key distinctions: first, DISH produces flowing anterior spinal ossification involving at least four contiguous vertebrae, but the sacroiliac joints are spared — in AS, the SI joints are the primary site of involvement and show sacroiliitis or fusion. Second, DISH patients have no inflammatory features (no elevated CRP, no morning stiffness, no response to NSAIDs) and are not HLA-B27 associated. Third, DISH is typically seen in older, often obese, diabetic men — AS presents in young adults under 40. Fourth, the syndesmophytes of AS are delicate, vertical, marginal bony bridges (at the discovertebral junction), whereas DISH produces bulky, flowing anterior ossification (at the anterior longitudinal ligament). [1]

On this patient's radiograph, the bamboo spine with bridging syndesmophytes and fused sacroiliac joints is classical AS, not DISH."* [1]

Examiner: "What would you do if this patient presented after a fall with back pain?" [1]

"This is a medical emergency. The fused bamboo spine is brittle and osteoporotic — it behaves like a long bone rather than a flexible column. Even a low-energy fall from standing height can cause an unstable three-column fracture, typically at the cervicothoracic or thoracolumbar junction, with a high rate of neurological deficit and mortality. [1]

My approach: first, immobilise the patient on a spinal board immediately and maintain cervical spine precautions. Second, image the full spine with CT (not just the area of pain — the fracture may be distant from the symptomatic site). Third, if CT shows a fracture or if there is any neurological deficit, proceed to MRI to assess cord compression and ligamentous injury. Fourth, urgent spinal surgery or neurosurgery opinion — many of these fractures require operative stabilisation because the long fused lever arm makes non-operative management hazardous. Fifth, admit for observation and neurological monitoring.* [1]

The key teaching point: never dismiss back pain after a fall in a patient with ankylosing spondylitis as a simple flare — always image the full spine."* [1]