Clinical case 1

An 83 year-old man was hospitalized with progressive mechanical lumbar and sacral pain, without any history of trauma.
In 2001, he was diagnosed to have a paraneoplastic form of dermatopolymyositis due to prostatic adenocarcinoma and
received treatment with corticosteroids and azathioprine.

1. What one thing would you do next?

a. Write a prescription for paracetamol and tramadol and control in one month
False. Although it is important to reduce pain, the history of the patient may indicate another cause of lumbar pain that
would deserve a more specific treatment.
b. Continue your history taking and make a clinical examination
True. It is important to know more about his symptoms and his physical examination.
c. Order an x-ray of the spine
False. An X-ray is probably going to be part of the evaluation, but only after you have a clinical hypothesis.
d. Increase the corticosteroids dosage
False. Definitely not. There is no reason to think about a flare of his dermatopolymyositis.
e. Organize blood exam in emergency
False. Blood tests are not relevant at this stage to make a diagnosis.
There was no weight loss, and the pain was clearly mechanical. The physical examination demonstrated local pain on
palpation of the lumbar and sacral region, with limited motion of the lumbar spine. There were no neurological signs
except a moderate quadriceps atrophy. The laboratory exams showed a normal ESR and C-reactive protein, and
normocytic anaemia at 108 g/l. Creatinine was measured at 110 mol/l (clearance 40 ml/minute). Alkaline phosphatase
was slightly elevated, but calcium levels were normal.
2. What two things would you do at this stage?
a. Reassure the patient and tell him to come back in 4 weeks if the pain is not improved
False. Although the first laboratory exams and CRP are normal, a specific cause of low back pain is certainly not
excluded. In this clinical setting, further investigations are warranted, and this patient deserves at least a symptomatic
treatment.
b. Write a prescription for paracetamol and tramadol
True. Further investigations are warranted to try to obtain a definite diagnosis to improve the treatment. However, there
is no contra-indication to a symptomatic treatment in the meantime.
c. Prescribe NSAIDs
False. Symptomatic treatment is warranted, but NSAIDs have no added value in this case over paracetamol and
tramadol, while they are contra-indicated in the presence of renal insufficiency.
d. Order both a dosage of prostatic specific antigen and bone scintigraphy
False. Dosage of the prostatic specific antigen (PSA) is certainly sensible in an older male with low back pain and an
history of prostatic cancer, but the bone scintigraphy should be delayed until a specific need is confirm: detection of
metastasis if PSA values are high or a high suspicion of fracture not demonstrated on regular x-rays.
e. Prescribe physiotherapy
False. Physiotherapy should be reserved until the diagnosis has been ascertained and infection, fractures or metastasis
excluded.

f. Order plain AP and lateral lumbar spine x-rays

True. It is important to definitely rule out other pathological cause of low back pain in a patient with multiple "red flags"
and fractures and metastasis come high in the list with patient on corticosteroids and known for a prostatic
adenocarcinoma.
g. Order an RMI of the spine
False. Initially it is important to rule out major pathological abnormalities with standard x-rays. RMI should be reserved at
cases where infection is highly suspicious (much higher sensitivity) or later one, when evolution is unsatisfactory.
h. Order a dosage of CK and aldolase
False. History and physical exam are not suggestive of relapse of his dermatopolymyositis.
i. Order a serum protein electrophoresis
False. Multiple myeloma has to be excluded in the presence of fractures and high ESR, which is not the case of our
patient. Furthermore, simple serum electrophoresis is not good to exclude multiple myeloma. One should order an
immunofixation test as well as a urine search for light chain.
The standard x-ray of the lumbar spine and pelvis demonstrated degenerative changes with disc arthrosis and
zygapophyseal osteoarthritis, but no sign of vertebral fracture, infection or metastasis.
3. What would you prescribe at this point (give your two best choices)?
a. Paracetamol
True. Almost always a good choice, even if you can expect if could be insufficient. It is the first step in pain
management.
b. NSAIDs
False. Preferably not. NSAIDs are good analgesic, and usually better than paracetamol for most patients. However, in
an older individual with kidney failure and corticosteroids treatment, this is asking for trouble. Use it only with a lot of
caution.
c. Oral steroids
False. Certainly not. This is not a flare of his connective tissue disease and corticosteroids have no value in the
treatment of low back pain.
d. Tramadol
True. Another good choice, particularly in this case where the use of NSAIDs is relatively contra-indicated. Tramadol is
the next logical step after paracetamol, and it would appear wise to prescribe both as paracetamol alone is unlikely to be
sufficient in such a patient.
e. Morphine or another major opioid
False. Not at this point. Morphine and other major opioids are very good analgesics and should be used if needed.
However, their use should be limited to very severe acute pain or in their regular place in the management of pain, when
the first steps failed.
f. Amitriptyline or another antidepressant
False. Not at this point. If antidepressants have a place in pain management, it is very limited in low back pain as
demonstrated by a meta-analysis.
g. Gabapentin or pregabalin
False. Gabapentin or pregabalin are registered for the management of neuropathic pain such as diabetic painful
neuropathy or postherpetic pain syndrome, which is not the problem. Our patient has a typical mechanical pain.
The patient did not improve with paracetamol and tramadol despite increasing tramadol to the maximal tolerated dose.

The pain worsened in general. Finally, the patient was incapable of getting out of bed. In the setting of mechanical pain
and corticosteroid treatment, a fracture was most likely, despite normal X-rays.
4. At this point, which elements of history, physical examination and laboratory tests would exclude a
pathological fracture?
1.Absence of weight loss
2.Absence of fever
3.Normal standard x-rays of the lumbar spine and pelvis
4.Elective pain on percussion of dorso-lumbar junction
5.Normal calcaemia
6.Decrease pain in supine position
7.Normal prostatic specific antigen level

Answer :
Q1. No. Weight loss is a non specific symptom and if a weight loss of >4.5 kg in 6 months is suggestive of cancer, its
absence doesn't exclude it at all. The presence of history of cancer by itself makes the diagnosis highly likely and
deserves a thorough workout.
Q2. No. Like weight loss, fever is a non specific symptom. Furthermore, overt fever is rare in cancer. It would rather
suggest an infectious process.
Q3. No. Remember that at least 30% of the bone mass has to be destroyed to be apparent on standard x-rays.
Q4. No. Elective pain is totally non-specific and may be present in any condition associated with back pain, from very
worrisome to totally benign.
Q5. No. Elevated calcium level may be the sign of vertebral metastatic disease, multiple myeloma and
hyperparathyroidism, but its negative predictive value is certainly very low.
Q6. No. Pain not responding to rest is quite sensitive for cancer, but the opposite is not true and it doesn't allow out
cancer to be ruled out.
Q7. No. A normal PSA level is reassuring in this setting. However, it doesn't rule out prostatic cancer and, in particular, it
doesn't rule out another type of cancer.
We performed an MRI of the sacrum which demonstrated a typical sacral fracture in H, without evidence for metastatic
disease.
5. What one thing would you do at this stage?
a. Add aspirin, up to 4 grams a day to the current analgesic treatment.
False. Definitively not. NSAIDs are contra-indicated in this patient, but aspirin is even worse in a patient under
corticosteroids with an elevated risk of gastrointestinal bleeding.
b. Prescribe intravenous bisphosphonates.
False. Bisphosphonates are a good treatment for osteoporosis, but they have no place in the pain management of
osteoporosis fractures.
c. Prescribe intranasal calcitonin.
False. Calcitonin is a treatment of osteoporosis and has some pain modification effect. However, they are best regarded
as an adjunct to regular analgesic therapy.
d. Prescribe a cimentoplasty.
False. Percutaneous cementoplasty under CT or fluoroscopy control are becoming increasingly popular. They do have a
place in vertebral fractures and they appear to be also efficient in sacral fractures such as in this patient. However, they
should be reserved to patients who do not respond to well conducted pain therapy with major analgesics.
e. Prescribe morphine or another major opioid
True. Morphine would be the next step of pain control, after failure of paracetamol and tramadol at maximal dosage.

Conclusion : Oral morphine was introduced at a dose of 30 mg per day. The patient rapidly developed severe nausea
and vomiting, with secondary dehydration and acute renal insufficiency which necessitated parenteral hydration.
Sublingual buprenorphine was also tried, but rapidly interrupted after nausea and an acute confusional state developed.
Because of persistent and invalidating sacral pain, we finally performed a sacral cementoplasty under CT guidance. The
patient improved over the next 48 hours, allowing for rapid mobilization and physiotherapy. The patient was discharge
within the week.
Clinical case 2
The patient is a 54 year old female accountant treated successfully over the last 4 years with adalimumab for a
diagnosis of ankylosing spondylitis associated with ulcerative colitis. She now complains of severe lower lumbar and left
buttock pain, which appeared over the last 3 weeks without any triggering event.

1. What would you do?

a. Reassure the patient, tell her that flares are common and setup another appointment in 3 months
False. Although it is potentially a flare, numerous other diagnoses have to be entertained. It would be ill-advised to leave
somebody on biologics without exploring further possible diagnoses.
b. Prescribe additional NSAID at full dosage for a flare
False. If the prescription of a symptomatic treatment has to be considered, it would be ill-advised to start such treatment
without exploring the aetiology of the symptoms.
c. Continue with questioning and clinical examination
True. Of course! We still know too little about the patient and her complaints to decide on the next step.
d. Immediately order pelvic or sacroiliac x-rays and see her again with the results
False. Ordering a specific test should be guided by your clinical hypothesis to optimize your management. Do you
already have a consistent one?
e. Switch to another anti-TNF agent such as infliximab or etanercept
False. Treatment should also be guided by clinical hypothesis. There is no single reason to plan a switch of anti-TNF at
this point.
For the patient, the pain is not quite similar to previous episodes of sacroiliitis. It has a burning sensation and radiates to
the side of the thigh and leg and then to the inside of the foot. There is both a mechanical and inflammatory component
to the pain, and the pain is aggravated by sitting. There is no fever, weight loss or other "red flags", but she is known for
a history of uterine cancer considered as cured 15 years ago. She admits to being under a lot of stress at work lately,
but denies any gastrointestinal flare of her ulcerative colitis. She has not observed any disturbances of sensitivity or
weakness in the lower limbs.
2. At this point, which diagnosis do you entertain? Write down the arguments in favour or against the following
diagnoses and grade their likelihood.
1.Inflammatory sacroiliitis
2.Infectious sacroiliitis
3.Disk hernia with radicular pain
4.Discitis or psoas abscess
5.Zoster pain
6.Metastasis or primary tumour of the spine
7.Visceral referred pain
8.Functional pain

Answer :
Q1: possible. She is known for ankylosing spondylitis and sacroiliitis. However, she was successfully treated for this
condition until now without complaint and the history is not typical, with no inflammatory back pain that would hint at an
active spondyloarthropathy. Furthermore, sacroiliac joint pain extends to the leg, but not lower than the knee.
Q2: possible. Previous inflammatory sacroiliitis does not prevent infection, and probably increases the overall risk.
Furthermore, she is treated with anti-TNF and one should always entertain infection in such context, in particular with
atypical germs such as tuberculosis. Absence of fever, real inflammatory pain and pain extending down to the foot
decreases its likelihood. Nevertheless, a sacroiliac abscess could also cause a peripheral neuropathy.
Q3: most likely simply by its frequency alone and the description of a radicular L5 syndrome without real "red flags".
Q4: unlikely. Low probability in the absence of fever, put possible again in the context of an anti-TNF treatment.
Ulcerative colitis is a risk factor for psoas abscess. Both diagnoses could explain a radicular syndrome.
Q5: possible. Zoster can certainly mimic a disk hernia with radicular pain. Anti-TNF treatment increases the likelihood.
One would expect perhaps a more neuropathic pain and the description of a skin rash. However, skin lesions can be
easily overlooked by patients.
Q6: unlikely. 54 years of age and a previous history of cancer are in favour of such a diagnosis, in particular metastasis.
Nevertheless, the probability is low.
Q7: unlikely. The diagnosis of referred pain from a visceral origin should always be entertained in low back pain.
However, there is no history to favour such a diagnosis and radicular pain would be atypical.
Q8: no. At this point, functional pain is a diagnosis of exclusion in a patient with ankylosing spondylitis treated with
anti-TNF. Other diagnoses have to be entertained and excluded before such a diagnosis is made.
At clinical examination, she appears in pain, but otherwise is in good general condition. There is no fever, adenopathy or
skin eruption. She walks with a limp, but the musculoskeletal examination fails to reveal any signs of peripheral arthritis
or enthesitis. There is tenderness over the left buttock, without clinical signs of sacroiliitis. Tendon reflexes are present
and symmetrical, and there is no demonstrable motor or sensory deficit. Straight leg raising is positive at 45 .
3. What exam would be most useful at this point?
a. Standard AP and lateral lumbar spine radiographs
False. Standard AP and lateral lumbar spine radiographs are recommended in the presence of low back pain and "red
flags". Their purpose is to exclude obvious fractures, discitis or metastasis destroying most of a vertebra, a very unlikely
diagnosis in our patient. The probability that this exam gives us a clue is extremely low.
b. Standard AP pelvis and specific sacroiliac joint incidence radiographs
False. We know our patient suffers from ankylosing spondylitis, we expect sacroiliac joints abnormalities. This exam has
no added value.
c. Sacroiliac joint RMI
False. A MRI of the sacroiliac joint would confirm an active sacroiliitis (infectious or inflammatory) if positive. However,
both diagnoses are low in our diagnostic list.
d. Sacroiliac joint CT
False. Not much better than a plain x-ray of the sacroiliac joint. We know our patient suffers from ankylosing spondylitis
and we expect sacroiliac joints abnormalities. This exam has no added value but perhaps in the totally unexpected case
of an infectious sacroiliitis with a demonstrable abscess.
e. Blood routine with ESR and CRP
True. Of course! Our most likely diagnosis is a disk hernia with radicular syndrome. However, normal ESR and CRP
would even further decrease the likelihood of an infectious problem, a problematic that must always keep in mind in the
context of immunosuppressive therapy.
You perform a routine laboratory investigation, which fails to reveal overt signs of inflammations with a normal
sedimentation rate and CRP at 5 mg/l. You decide to wait and see and not to order other exams for the moment.
4. What would you prescribe at this point (give your three best choices)?

a. Paracetamol
True. Almost always a good choice.
b. NSAIDs
False. Preferably not. NSAIDs would be an excellent choice in a patient with ankylosing spondylitis or with a radicular
pain syndrome. However, in this case, the history of ulcerative colitis (UC) should make you cautious. NSAIDs are well
known for their gastric toxicity. However, they also display a definitive toxicity for the small bowel and colon and should
be avoided if possible in Crohn's disease and UC because of the risk to induce a flare.
c. Coxibs
True. Coxibs are not your best choice, but highly selective coxibs such as etoricoxib would present the advantages of
NSAIDs while minimizing the risk to induce a flare of the IBD.
d. Oral steroids
False. Certainly not. Oral corticosteroids have no demonstrated value in ankylosing spondylitis and low back pain with
radicular pain syndrome.
e. IV steroids
False. Certainly not. IV corticosteroids have limited value in some rare case of severe and very active ankylosing
spondylitis, an unlikely diagnosis, while they have no room in low back pain with radicular pain syndrome.
f. Tramadol
True. Another good choice, in particular in this case where the use of NSAIDs or coxibs is limited by the history of IBD.
Tramadol is the next logical step after paracetamol, and it would appear wise to prescribe both as paracetamol alone is
unlikely to be sufficient in such patient.
g. Morphine or another major opioid
False. Not at this point. Morphine and other major opioids are very good analgesics and should be used if needed.
However, their use should be limited to very severe acute pain or in their regular place in the management of pain, when
the first steps failed.
h. Switch to infliximab
False. Switching between anti-TNF can be useful in both primary and secondary anti-TNF failures, but this is not the
problem at hand.
i. Tryptizol or another antidepressant
False. Not at this point. Antidepressants are indicated in pain management for neuropathic pain or when overt
depression is present, which is not the case. Their effect size is limited and they are best seen as adjunct to other
therapy.
j. Gabapentin or pregabalin
False. Not at this point. Gabapentin or pregabalin are registered for the management of neuropathic pain such as
diabetic painful neuropathy or post herpetic pain syndrome, which is not the actual problem. They have no demonstrate
role in the management of another type of acute radicular pain syndrome.
You see her 6 weeks later. She is still very symptomatic despite paracetamol and etoricoxib. She has tried tramadol,
which was moderately effective but caused severe nausea. She suffers from some low back pain, but mainly from leg
pain with a L5 root territory. There is no obvious neurological deficit.
You perform an MRI of the spine and the pelvis with T1, T2 and gadolinium enhanced sequences. This exam
demonstrates bilateral sacroiliitis, but without any signs of activity. There is no abscess, signs of infection or evidence of
cancer. There is no disc hernia or significant disc disease.
5. What exam would you consider most useful at this point?

a. Bone scan with technetium

False. Sensitivity of bone scan is good for infection and osteoblastic metastasis, while it is probably overrated for
inflammatory sacroiliitis. In all cases, it doesn't perform better than MRI and it would be useful only if sites of involvement
were not studied by your MRI, a very unlikely proposition.
b. Psychological evaluation
False. A psychological evaluation could be of therapeutic value in the management of pain. However, there is little place
for such evaluation in the diagnosis workout in a patient without signs of simulation or hysteria.
c. PT - scan CT
False. The value of PT-scan CT lies in the search of metastatic diseases or perhaps major arteries inflammation, both
problems very unlikely in our situation.
d. Neurologic consult with an EMG
True. A good choice! Your patient suffers from leg pain with a radicular L5 territory, but without demonstrable
compression of the nerve root. An EMG could confirm, after this lapse of time, the radicular involvement and distinguish
it from a peripheral nerve involvement. Finally, it can give some clues on the aetiology of such involvement.
e. Cerebral MRI
False. Fishing expedition! There might be a rare painful syndrome due to thalamic involvement for example. However,
there is no hint this could be potentially the case. Drop it!
A neurological consultation with EMG clearly demonstrated a L5 root lesion with chronic and subacute signs of
denervation. A new lumbar MRI was performed, which again failed to demonstrate any signs of disc hernia, but clearly
showed a well localized L5 nerve root inflammation (see figure 1). A thorough workup failed to demonstrate an aetiology
for this finding, in particular no infectious or paraneoplastic causes. She is still very symptomatic and unwell with her
current treatment.
6. What drugs could you add to your prescription, with some evidences to defend it, at this point, and in what
order?
a. Oral steroids
False. No evidence! Demonstration of some inflammation doesn't mean it will respond to corticosteroids. Desperation
could urge us to try such treatment, you need however to recognize the fact.
b. IV steroids
False. Same think. An IV line makes it a better placebo in this setting, but it doesn't make it a better choice.
c. Morphine or another major opioid
True. A good choice! The patient is very symptomatic and need pain relief. Morphine and other major opioids are
effective analgesics and should be used when paracetamol, NSAIDs and weak opioids have failed.
d. Amitriptyline or another antidepressant
True. A possible choice. Antidepressants have a place in pain management. However, a meta-analysis has
demonstrated that their role in chronic low back pain is certainly limited.
e. Gabapentin or pregabalin
True. Another good choice. Even if she doesn't have diabetic or post herpetic neuralgia, pregabalin has been registered
for neuropathic pain, which is certainly the case in our patient. It appears worth a try.
f. Foraminal infiltration
False. No evidence again! Percutaneous periradicular foraminal steroids infiltration under CT control are becoming
increasingly popular. However, data on efficiency are still scant and limited to cases with nerve root compression. If it
appears sensible to try such procedures in this patient, you should nevertheless recognize the fact that there is simply

no evidence, and inform your patient of it.

Conclusion : Various opioids were carefully tried in this patient with severe nausea under tramadol. Oxycodone
appeared to be more effective and better tolerated than tramadol, but was nevertheless insufficient to really relieve the
patient.
On the contrary, pregabalin was extremely effective. However, its use was limited by severe intolerance in the form of
fatigue and an incapacity to concentrate, rendering the patient unable to pursue her professional activity with this
treatment.
Finally, a percutaneous periradicular foraminal steroid infiltration under CT guidance control was performed despite the
absence of any evidence. This procedure was moderately effective with an estimated benefit of 30%.
At 6 months, she still suffers from a chronic pain syndrome, but has been able to resume her professional activities
under a combination of paracetamol, etoricoxib, oxycodone and low dose pregabalin.