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