Another Case of Low Back Pain Kristin Etzkorn, DO Georgia Regents University Augusta, GA
Dec 25, 2015
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