Clinical case 1

A female patient, aged 29 years, presents for the first time. She works as a cleaning lady. For 2 years she has
experienced several episodes of low thoracic pain which last maximally 3 weeks. There was no prior trauma and the
complaints had a gradual onset. She awakes because of pain between 4 and 5 am. During such a pain episode she
isnt able to work.
The patient is evaluated by a rehabilitation medicine doctor. A physical examination shows no specific abnormalities.
Additional examinations are performed :
- Laboratory : HLA B27 negative
- MRI lumbar spine (with focus on the medulla) : intervertebral disc bulging L4-L5
- Electromyography of the lower limbs : normal

1. What would you give as first therapy?

a. Start analgesic therapy
False. There is no evidence for the efficacy of therapy with analgesics in patients with IBP. Furthermore, when in doubt
about the inflammatory character of the pain, treatment with analgesics does not provide any useful information
b. Start NSAID therapy
True. In case of back pain of inflammatory character NSAIDs are the first choice therapy. A good response of NSAIDS
is included in the ASAS Classification criteria for axial Spondyloarthritis (axSpA), and therapy with an NSAID would in
this case also provide valuable diagnostic information. In about 70% of the SpA-cases, NSAIDs will have a beneficial
effect, when given at a daily maximally tolerated anti-inflammatory dosage.
c. Prescribe physical therapy
True. Physical therapy has been proven effective in patients with axial Spondyloarthritis. It is an important additional
therapy that should be introduced in a symptomatic patient.
d. Start sulfasalazine
False. There is no evidence for DMARDs to be effective in axial disease of SpA.
e. Start high dose corticosteroids
False. There is no evidence for corticosteroids at a low or moderate dose to be effective in axial disease of SpA.
Unfortunately, it was decided to treat the patient with analgesics and muscle relaxants, which did not provide any
amelioration (apart from minor pain relief during 1 or 2 days). The patient is now complaining of daily lumbar pain, with
irradiation to the right buttock. She awakes systematically at night, and there is a clear history of morning stiffness,
which improves with movement. The pain is returning during the day when she has to sit for more than one hour. The
physical examination shows only a minor restriction of lumbar mobility. A repeat MRI focused on the lumbar spine,
reveals again bulging of the intervertebral disc L4-L5 with possible herniation.
2. What would you do now?
a. Start NSAID therapy on demand.
False. As a diagnostic test the use of NSAIDs on demand will not provide useful information.
b. Give epidural corticosteroid infiltrations L4-L5.
False. As there are clinically no obvious signs of lumbar nerve root compression, epidural corticosteroid injections are
not indicated.
c. Start NSAID therapy at maximal tolerated anti-inflammatory dose.
True. NSAID therapy at a maximal tolerated anti-inflammatory dose is the cornerstone of treatment of axial disease in
SpA. In this case, it would also provide useful diagnostic information regarding the therapeutic response to this

treatment.
d. Start combination of NSAID and sulfasalazine.
False. There is not much evidence for DMARDs to be effective in axial disease of SpA.
e. Refer the patient for surgical treatment of the intervertebral disc problem.
False. Although there is some doubt on imaging about a possible herniated intervertebral disc L4-L5, the clinical
presentation does match this finding and electromyography of the lower limbs was normal. This patient is not a
candidate for surgery!
f. Perform diagnostic work-out.
True. Since there is still no diagnosis, a further work-out should indeed be performed.
After referral to a rheumatologist, therapy is started with diclofenac slow release 75 mg twice daily, which provides rapid
relief of nocturnal pain and improvement of morning stiffness.
Clinical examination reveals a slightly decreased axial mobility with chest expansion 4 cm and modified Schobers
test 10/13,5 cm. Upon skin examination, discrete psoriatic lesions are noted behind the ears. Family history is positive
for SpA; the father of the patient also has psoriasis.
Laboratory examination reveals a normal erythrocyte sedimentation rate (4 mm/1st hour) and a normal CRP 0,3 mg/dl
(normal values less than 0,5 mg/dl).
MRI of the sacroiliac joints shows minimal bone marrow oedema right-sided on T2-weighted, fat-suppressed images. No
structural lesions of the sacroiliac joints could be seen.
3. What is the most appropriate therapy?
a. Continue NSAIDs at maximal tolerated anti-inflammatory dose.
True. In this patient a diagnosis / classification of early 'non-radiographic' SpA can be established based on the
presence of acute sacroiliitis lesions on MRI and at least 2 additional SpA features (inflammatory back pain, response to
NSAIDs, psoriasis). In psoriatic axial disease the prevalence of HLA B27 is lower compared to classic AS. NSAIDs are
the cornerstone of medical treatment. They should preferentially be given at a daily full anti-inflammatory dose. In case
of intolerance or side effects, (1) dose tapering, (2) change of NSAID, or (3) addition of a proton pump inhibitor might be
considered.
b. Start TNF-alpha blocking therapy.
False. Before prescribing TNF-alpha blocking agents, a maximally tolerated anti-inflammatory dosage of at least two
NSAIDs should be tested over a period of at least 1 month.
c. Give CT-guided intra-articular injection of corticosteroids in the right SIJ and keep NSAID dosage as it is.
False. In small RCTs the (CT-guided) intra-articular injection of corticosteroids has been shown to be effective for the
pain of sacroiliitis. In this case the pain responded well to NSAID therapy, and so the presence of sacroiliitis on MRI has
at this moment only diagnostic value. If the patient would experience predominant symptoms of sacroiliitis, this
treatment approach could be chosen.
d. Start Sulfasalazine.
False. There is no evidence for DMARDs such as Sulfasalazine or Methotrexate to be effective in axial disease of SpA.
e. Start Methotrexate.
False. There is no evidence for DMARDs such as Sulfasalazine or Methotrexate to be effective in axial disease of SpA.
Axial symptoms remain well controlled for approx. 7 months. There are no signs of peripheral joint, enthesis or dactylitis
involvement. However, skin psoriasis is gradually worsening with approx. 10% of the body surface area affected, and
despite continuous intake of NSAIDs and regular physical therapy, the patient develops again significant inflammatory
pain at the thoracic level. A change from diclofenac to piroxicam 20 mg daily does not provide any relevant symptom
relief. The BASDAI is elevated with a value of 6 (on a 0-10 Numeric Rating Scale).

MRI of the spine reveals multiple inflammatory vertebral lesions (Romanus lesions) at the thoracic level.
4. What would you do now?
a. Change to another NSAID at full anti-inflammatory dose.
False. The patient already received 2 NSAIDs at full anti-inflammatory dose. Although switching to yet another NSAID
could theoretically still provide clinical benefit in a (small) number of patients, the likelihood of a good response is small.
b. Start corticosteroids.
False. There is no evidence for corticosteroids at a low or moderate dose to be effective in axial disease of SpA.
c. Start methotrexate as DMARD for psoriatic arthritis.
False. Although methotrexate is used to treat peripheral joint disease and skin involvement in psoriatic arthritis, there is
no evidence for any DMARD (sulfasalazine, methotrexate) to be effective in axial disease of SpA. In case of arthritis in
addition to the axial disease a 3 month therapy with sulfasalzine can be effective.
d. Start TNF-alpha blocking therapy.
True. In patients with active axial SpA (BASDAI >4), not responding to maximal tolerated anti-inflammatory dosage of at
least 2 different NSAIDs, anti-TNF therapy is indicated. A good clinical response both on axial disease and skin
involvement might be expected.
Clinical case 2
A young man of 18 years presents with an atraumatic swelling and inflammatory pain of the left ankle. He had no
previous medical history.
He had a fever of 38C and felt sick two weeks ago. His inflammatory parameters are significantly raised.

1. What would be your two first steps?

a. Administration of an antipyretic drug
False. This medication only has a restricted symptomatic effect (especially when the cause would be underlying
inflammation. Moreover, an eventual response to treatment (e.g. less pain)will not help in establishing a diagnosis.
b. Start antibiotics
False. Diagnosis of septic arthritis is not made. Administration of antibiotics could make culture of joint fluid or blood
negative, so that in case this would be a septic arthritis the responsible microbial agent would remain unknown and
correct antibiotic treatment impossible
c. Administration of NSAID
False. Administration of an NSAID could have a beneficial effect on the pain, but will not help in making a final
diagnosis. However, a good response might suggest an inflammatory condition such as SpA.
d. Make an evacuating joint puncture of the left ankle for joint fluid examination and culture; if culture is negative inject
corticosteroids
True. By examining the joint fluid differential diagnosis between an infectious arthritis, a crystal induced arthritis or
another inflammatory disease would be possible. Injection of corticosteroids, in case of negative culture, will be highly
efficacious.
e. Start corticosteroids
False. Administration of corticosteroids will not help in establishing a diagnosis, could have important side-effects and
would jeopardize definite diagnosis (by having a profound but temporary effect on clinical examination, lab
abnormalities).

f. Perform diagnostic work-up

True. Since there is no definite diagnosis, a further work-up should indeed be performed.
Joint fluid examination revealed an inflammatory synovitis; examinations for crystals and bacterial culture were negative.
Urine culture showed on PCR positivity for Chlamydia trachomatis. The synovitis of the left ankle disappeared, but 2
weeks later he developed a relapse of arthritis of the left ankle, arthritis of the right knee and tendinitis of the left Achilles
tendon. The radiographs showed normal sacroiliac joints and the patient was tested positive for HLA-B27.
2. What would be your two treatment choices?
a. Start NSAID at an anti-inflammatory dose
True. A diagnosis of SpA (reactive arthritis) is suspected. NSAIDs are the cornerstone in the treatment of SpA. In about
70% of cases NSAIDs will have a beneficial effect, and absence of response would prompt a reappraisal of the
diagnosis.
b. Start systemic corticosteroids
False. Administration of systemic corticosteroids have been described to be only slightly effective in SpA;. There are no
trial data on corticosteroids but they could be tried if NSAIDs failed.
c. Start methotrexate
False. There are no clinical trial data on the use of methotrexate in SpA. As such this treatment is not recommended. In
daily practice this agent might be used in case of oligo-articular peripheral arthritis not responding to NSAIDs and
sulfasalazine. Methotrexate might be considered first-line in case of more poly-articular disease.
d. Start sulfasalazine
False. Although some data exists that sulfasalazine can be beneficial for peripheral arthritis in SpA, one should try
NSAIDs first.
e. Give an intra-articular injection of corticosteroids in ankle and knee
True. In case of mono- or pauciarticular disease and after exclusion of septic arthritis, the use of local (intra-articular)
corticosteroid injections might be considered (especially in case of contra-indication or intolerance to NSAIDs).
f. Start antibiotics
False. No convincing data exists that antibiotics could have a beneficial effect for peripheral arthritis in patients with
reactive arthritis. Although the Chlamydia trachomatis infection should be treated with antibiotics in this patient and a
screening for Chlamydia should be performed in the partners with whom the patient has had sexual contact.
Initially the patient had a good response on a maximally anti-inflammatory dose of NSAIDS.
Initially the patient had a good response on a full anti-inflammatory dose of NSAIDS. At follow-up, the patient developed
relapsing anterior uveitis and relapsing oligoarticular arthritis.
3. Which medical treatment would you administer now?
a. Stop NSAID and start systemic corticosteroids
False. Although corticosteroids could be effective topically for the uveitis, this drug will not prevent relapses of uveitis. It
has also no or only a small effect on the peripheral manifestations of the disease.
b. Stop NSAID and start sulfasalazine
False. Sulfasalazine could have some beneficial effect on the peripheral synovitis, and perhaps also an effect on the
prevalence of flares of uveitis; it has no proven effect on axial disease. As sulfasalazine has a slow onset of action, there
is no reason to stop the NSAIDs immediately (they could of course be tapered in case of subsequent remission under
sulfasalazine).
c. Add methotrexate to NSAID
False. Methotrexate has no proven effect on axial disease; there is also no proven effect on peripheral arthritis in SpA,

although it might be used in daily practice when other treatment options would have failed. There are no adequate
studies on the prevention of uveitis flares with methotrexate (although the drug is used by ophthalmologists for treatment
of severe therapy-resistant uveitis).
d. Add leflunomide to NSAID
False. Leflunomide : idem as for MTX.
e. Add sulfasalazine to NSAID
True. As mentioned in Q2 sulfasalazine could be beneficial for peripheral arthritis and perhaps uveitis.
5 years after the start of the symptoms, the patient developed an active and histologically proven Crohns disease.
The rheumatic problems are still active: hes now suffering predominantly from inflammatory low back pain with pain
at night and morning stiffness. New X-rays of the sacroiliac joints shows sacroiliitis grade II bilaterally. The BASDAI is
7/10. He frequently develops relapses of uveitis.
4. Which would be the next step in medical treatment?
a. Start azathioprine and corticosteroids
False. Azathioprine and corticosteroids could be indicated for his Crohns disease but will not have effect on the
axial disease.
b. Start TNF blocker infliximab or adalimumab
True. Infliximab or adalimumab would probably have a marked and fast beneficial effect on his Crohns disease as
well as his rheumatic manifestations. Moreover, there are arguments that these drugs could reduce the frequency of
relapses of uveitis.
c. Start TNF blocker infliximab together with MTX
False. In rheumatoid arthritis the association of TNF-blocker with MTX is better than TNF-blocker alone. This has never
been proven for AS and axial Spondyloarthritis. There is currently no evidence that MTX, possibly by preventing the
formation of antibodies against the TNF-blocker, would influence the effect of the TNF-blocker. Moreover. administration
of MTX could induce side-effects.
d. Start TNF-blocker etanercept
False. Although Etanercept has been proven to be very effective for AS, this type of TNF-blocker has no effect on
Crohns disease and could even cause relapses of the intestinal symptoms. It also reduces flares of uveitis but more
relapses are seen under treatment with etanercept in comparison with the monoclonal antibodies blocking TNF.
e. Start MTX together with corticosteroids
False. Methotrexate and corticosteroids could be indicated for his Crohns disease and might be beneficial in
suppressing uveitis, but will not have an effect on the axial disease.
The patient had an excellent response to Infliximab; he went into remission both for his AS (BASDAI 1-6/10) and for his
Crohns disease. During the 4th infusion the patient developed a relevant allergic reaction with hemodynamic
instability (hypotension) Infliximab was stopped but after 2 months he developed a relapse of both his axial disease and
of his Crohns disease.
5. Which medical treatment would you start?
a. Start etanercept
False. Although Etanercept has been proven to be very effective for AS, this form of TNF-blocker has no effect on
Crohns disease and could even cause relapses of the intestinal symptoms. It also reduces flares of uveitis but more
relapses are seen under treatment with etanercept in comparison with the monoclonal antibodies blocking TNF.
b. Start adalimumab
True. Adalimumab has been proven to be effective in active Crohn's disease and in active AS. There is also efficacy on

uveitis.
c. Start adalimumab + MTX
False. MTX would not add anything to the effect of adalimumab and could cause side-effects.
d. Give a pulse of corticosteroids
False. Pulse corticosteroids could stop temporarily the relapse of Crohn's disease but would only have a slight effect at
most on axial disease.
e. Restart infliximab with steroid pre-medication
True. A re-infusion with Infliximab can be considered with steroid pre-medication on condition there will be a strict
monitoring of the vital signs.