Handout

6/14/2013
Financial Disclosures
• Nothing to disclose
Another Case of Low Back Pain
Kristin Etzkorn, DO
Fellow
GRU
CC: Low back pain
Review of Systems
• HPI: 55 y/o white female
– Low back and cervical pain and stiffness
– 20 lb. unintentional weight loss x 1 year,
+ fatigue, decreased appetite
– No changes vision, no history uveitis
– Dyspnea on exertion
– No chest pain, edema
– Color changes noted on hands and ears
– Bruising tendency
– Joint pain, no swelling
– No changes in urination
– Anxiety, depression
• Improved with activity and heat
• Morning pain lasting 2-3 hours
• Moderate relief w Percocet, Aleve, Nabumetone
– Knee pain bilaterally presented first
• X-ray consistent with OA
– Seen by neurosurgery with CT, MRI and
myelogram which showed stenosis of the cervical
spine and a “bamboo spine”
History
• PMH:
– Hemochromatosisdiagnosed by blood work,
not phlebotomized
– HTN
– Emphysema
– Sensory neuropathy
• FH:
– Mother: same arthritis and
involvement of her joints,
RA, possible AS, bone cancer,
emphysema
– Father: psoriasis, HTN,
esophageal cancer
Physical Exam
• PSH: Appendectomy
• Social: +tobacco abuse
• Meds:
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Naproxen 220mg
Caltrate 600 mg w/ D
Clonazepam 0.5mg
Melatonin
Neurontin 100mg
Percocet 5/325
Albuterol INH
HCTZ/Lisinopril 12.5/20mg
Nabumetone 750 mg
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96.7 121/68 93 20 BMI 22
Thin, AAOx3, NAD
PERRLA, EOMI, normal conjunctiva
OP clear
Supple, NT
CTAB, respirations non-labored
RRR, no m/r
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Laboratory Results
Physical Exam
• MSK:
– Limited abduction of the right shoulder
– Crepitus of the knees bilaterally, pain with full
extension
– Full ROM of all other joints, no swelling or deformity
– C-spine- natural position slightly flexed, cannot extend
beyond neutral,
– L-spine- cannot extend beyond neutral
– Schober- 1 cm increase on forward flexion opposed to
neutral back
– Levoscoliosis
140
105
13.2
23
121
4.5
32
0.48
244
5.9
38.7
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Calcium: 9.5
TP: 6.9
Albumin: 4.1
AST: 24
ALT: 12
Alk ф: 79
T. bili: 0.4
• ESR: 13
• Ferritin: 50
(normal 11-307)
• Transferrin: 220
(normal 200-360)
X-rays: C-spine
X-ray: C-spine
X-ray: C-spine
X-ray: Pelvis
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A.
B.
C.
D.
E.
F.
G.
X-ray: Pelvis
X-ray: L-spine
X-ray: L-spine, flexion/extension
X-ray: L-spine
What would you do next ?
Physical Exam
HLA-B27
Quantiferon gold and Hepatitis profile
Intact PTH
TSH
IGF-1
Ceruloplasmin
SPEP/UPEP
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X-ray: L-spine
Workup
• Urine screen for organic acids
– Significantly elevated excretion of homogentisic acid
– 2563 mmol/mol cr, reference value <11
Alkaptonuria
Name This Gentleman
• 1902- Sir Archibald Garrod
• Rare inborn error of metabolism, autosomal
recessive inheritance
– Annually 1 case per 250,000 to 1 million live births
Alkaptonuria
• Large quantities of HGA excreted
daily in urine
– 5-8 gm/dy
• Specimen dark iron oxide-like
discoloration when exposed to
sunlight or alkalized
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
Baeva et al. RadioGraphics 2011; 31:1163-1167
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6/14/2013
Ochronosis: Presentation
Ochronosis
• Accumulation in tissues of homogentisic acid (HGA)
and its metabolites
• Deposits in connective tissues and binds irreversibly
to them and stimulates degeneration
– High affinity for fibrillary collagens
• Blue-black discoloration of connective tissues
including sclera, cornea, auricular cartilage, heart
valves, articular cartilage, tendons, ligaments
• Pigmentation due to oxidation and polymerization of
HGA
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Dark pigmentation pinna, sclera, nasal ala
Darkening urine with exposure to air
Low back pain, stiffness, height loss
Hip and knee pain
Cardiac valve calcification and stenosis,
coronary artery calcification
• Renal and prostatic stones
Ryan, A. et al. NEJM 2012; 367:e26
Ochronosis: Pathology
Ochronotic arthropathy
• Manifestation of long-standing alkaptonuria
• Accumulation of pigment deposition in the joints of
the axial and peripheral skeleton
• Symptoms manifest in 3rd-4th decade
• Most common presentation is low back pain
– Long-standing pain and limited ROM in the spine and large
joints
– Severe degenerative arthritis and spondylosis
• More rapid progression in men than women
• H&E stain- extensive degenerative changes and
brown pigmented deposits
• Mechanism not fully understood of HGA
accumulation leading to ochronosis and arthropathy
Baeva et al. RadioGraphics 2011; 31:1163-1167
Ochronosis: Diagnosis
• Imaging with characteristic findings
• Measure excretion homogentisic acid in urine
• Characteristic findings on physical exam
Ochronosis: Imaging of the Spine
• Lumbar spine
affected initially
• Widespread
calcification of
intervertebral disks
• Narrowing
intervertebral
spaces
• Osteopenia
• Vacuum disk
phenomenon
Baeva et al. RadioGraphics 2011; 31:1163-1167
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6/14/2013
Ochronosis:
Imaging of the Peripheral Joints
Ochronosis: Imaging of the Spine
• Knee most commonly
involved
• Long standing
disease:
– Obliteration
intervertebral
spaces
– Marginal
intervertebral
osteophytes
– Joint involvement more
pronounced lateral
compartment
• Typically lack prominent
osteophyte formation
• Often see intra-articular
osteochondral fragments in
knees, hip, shoulder
• Degenerative changes of
the SI joints and pubic
symphysis
Baeva et al. RadioGraphics 2011; 31:1163-1167
Baeva et al. RadioGraphics 2011; 31:1163-1167
Differential Diagnosis
• Ankylosing spondylitis
– Loss of lordosis, disk calcification, end-plate changes
– Lack of erosions
• OA
– Unexpectedly advanced changes for the patient’s age
– Less predominance of osteophyte formation than of joint space loss
– Prominence of intra-articular osteochondral fragments
• Disk calcification- most characteristic finding of ochronosis
– Also seen in: Degenerative changes, trauma, CPPD, AS, hemochromatosis,
hyperparathyroidism, acromegaly, amyloidosis
Ochronosis: Treatment
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No medical treatment to prevent or slow progression
Education, PT
Analgesics
Dietary restriction
Antioxidants: Vitamin C , n-acetyl cysteine
Nitisinone
Joint replacement
Ochronosis: Treatment
Ochronosis: Treatment
• Antioxidants
• Dietary Restriction
– Restrict tyrosine and phenylalanine
– Significant reduction in HGA levels achieved in <12
y/o
– Not demonstrated in older patients
– Difficult to maintain
– Vitamin C
• Prevent oxidation HGA to
benzoquinones that form
deposits in cartilage and bone
• Prevent rather than treat
• Efficient if supplemented to
infants before the onset
ochronosis
• Dose 1gram/day recommended
for older children and adults
– n-acetyl cysteine
• In vitro shown to reduce HGA
polymerization and accumulation
• Combination with vitamin C may
be effective in preventing or
delaying ochronotic arthropathy
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
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Ochronosis: Treatment
Ochronosis: Treatment
• Nitisinone
• Nitisinone (Orfadinᴿ)
– Inhibitor 4hydroxyphenylpyruvate oxidase
– Drug approval in
2002 for hereditary
tyrosinemia
– 95% reduction in urinary and serum HGA
– Long-term randomized trial in 40 patients completed in
2009
• Primary outcome- total hip ROM
– Treatment group with gain 2◦ per year over the 3 years vs placebo group
average decline of 0.37◦/year
– Not statistically significant
• Secondary outcome- Schobers measurement of spinal flexion, 6minute walk times, timed get up and go
– No significant differences between the 2 groups
• No patients in treatment group progressed to aortic stenosis or
sclerosis
• Well tolerated
– No evidence prevents or reverses ochronosis
– Longer clinical trial indicated to demonstrate clinical
efficacy
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
References
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Baeva et al. RadioGraphics 2011; 31: 1163-1167
Capkin E., et al. Rheumatol Int 2007; 28: 61-64
Introne, et al. Mol Gen Metab 2011; 103(4): 307-314
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
Ryan, A., et al. NEJM 2012; 367: e26
Tinti, et al. J. Cell. Physiolo. 225:84-91, 2010
Zhao et al. Knee Surg Sports Traumatol Arthrosc
2009; 17: 778-781
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