Another Case of Low Back Pain
Kristin Etzkorn, DOGeorgia Regents University
Augusta, GA
CC: Low back pain
• HPI: 55 y/o white female– Low back and cervical pain and stiffness• 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”
Review of Systems
– 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
History
• PMH: – Hemochromatosis- diagnosed
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
• PSH: Appendectomy
• Social: +tobacco abuse • Meds:
– 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
Physical Exam
• 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
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
Laboratory Results
• 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)
140
4.5
105
32 0.48
23121 5.9
13.2
38.7
244
X-rays: C-spine
X-ray: C-spine
X-ray: C-spine
X-ray: Pelvis
X-ray: Pelvis
X-ray: L-spine
X-ray: L-spine, flexion/extension
X-ray: L-spine
What would you do next ?
A. HLA-B27B. Quantiferon gold and Hepatitis profileC. Intact PTHD. TSHE. IGF-1 F. CeruloplasminG. SPEP/UPEP
Physical Exam
Workup
• Urine screen for organic acids– Significantly elevated excretion of homogentisic acid – 2563 mmol/mol cr, reference value <11
X-ray: L-spine
Name This Gentleman
Alkaptonuria
• 1902- Sir Archibald Garrod • Rare inborn error of metabolism, autosomal
recessive inheritance– Annually 1 case per 250,000 to 1 million live births
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
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
Baeva et al. RadioGraphics 2011; 31:1163-1167
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
Ochronosis: Presentation• 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
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
Ochronosis: Pathology
• 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
phenomenonBaeva et al. RadioGraphics 2011; 31:1163-1167
Ochronosis: Imaging of the Spine
• Long standing disease: – Obliteration
intervertebral spaces
– Marginal intervertebral osteophytes
Baeva et al. RadioGraphics 2011; 31:1163-1167
Ochronosis: Imaging of the Peripheral Joints
• Knee most commonly involved– 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
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
• No medical treatment to prevent or slow progression• Education, PT • Analgesics• Dietary restriction • Antioxidants: Vitamin C , n-acetyl cysteine• Nitisinone• Joint replacement
Ochronosis: Treatment
• Dietary Restriction– Restrict tyrosine and phenylalanine– Significant reduction in HGA levels achieved in <12
y/o– Not demonstrated in older patients– Difficult to maintain
Ochronosis: Treatment • Antioxidants
– 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
Ochronosis: Treatment
• Nitisinone (Orfadinᴿ)– Inhibitor 4-
hydroxyphenylp-yruvate oxidase
– Drug approval in 2002 for hereditary tyrosinemia
Ranganath, LR, et al. J Clin Pathol 2013; 66: 367-373
Ochronosis: Treatment
• Nitisinone– 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, 6-minute 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
References
• 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