Metabolic and regulatory disorders of musculoskeletal system

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Objective

• Gout• Pseudogout• Muscular dystrophy

Gouty arthritis

Epidemiology

• Primary gout = 1.7 : 100,000 / year• Age < 50 yr. M > F• Age > 50 yr. M < F• BMI, Diet, Alcohol, diuretic drug, Lead

poisoning

Purine metabolism

Pathogenesis

Clinical manifestation

1. Asymptomatic hyperuricemia2. Acute gouty arthritis3. Intercritical gout4. Chronic gout tophi

Diagnosis• Gold standard : Joint fluid aspiration

• Lab : serum uric acid level, CBC, ESR, CRP

Polarizing Microscope

Radiographic study

• Useful for chronic tophaceous gout • seagull wing sign

Differential diagnosis

• Pseudogout (CPPD)• Septic arthritis

Associated disease

• Renal disease : Chronic urate nephropathy, Acute uric acid nephropathy, Uric acid nephrolithiasis

• Metabolic syndrome : Hypertension, Obesity, Hyperlipidemia, Insulin resistance, Coronary heart disease, Stroke, peripheral artery disease, Congestive heart disease

Acute gouty arthritis

Single joint Oligo-polyarticular joint

Intra-articular steroid injection or NSAIDs or

Colchicine

Renal or hepatic disease

Normal renal and liver function

NSAIDs Colchicine 0.6 mg * 3

Prednisolone30-60 mg/day thenTaper off in 2 wks.

Solumedrol IM, IV 100-150 mg/d * 1-2 days

Or

ACTH SC, IM, IV 25-40 IU q 12 hrs * 1-3 days

Taking oral medications

UnableAble

High risk for cardiac or GI toxicity

Low risk for cardiac or GI toxicity

Antihyperuricemic therapies

• Uricostatic drugs : Allopurinol*, Oxypurinol, Febuxostat

• Uricolytic drugs : Uricase• Uricosuric drugs : Probenecid**,

Benzbromarone, Sulfinpyrazole***, Losartan, Fenofibrate, Atorvastatin

Controversy

• Asymptomatic hyperuricemia

• Criteria for treatment : 1. At least two gout attacks/

year2. Chronic tophi3. Coexisting illnesses ex.

Nephrolithiasis

Chronic tophi treatment

• **Do not excision**• Biopsy only to confirm diagnosis• Check urine uric acid level 24 hr : Urate

overproduction Vs Urate underexcretion• Control serum uric acid level < 5 mg/dL

ACR recommendation 2012

Pseudogout

Definition

• CPPD (Calcium Pyrophosphate Dihydrate) Crystal Deposition Disease

• Acute form of disease

Common Clinical Presentations

Clinical setting

• Elderly age over 55 years• Mimic to gout• large joint, most often the knee • less often the wrist or ankle • provoked by minor trauma or intercurrent

medical or surgical conditions including pneumonia, myocardial infarction, cerebrovascular accident, and pregnancy.

• Parenteral G-CSF, Bisphosphanate

Natural history

• Chronic case turn to Chondrocalcinosis

Pathogenesis

• The loose avascular connective tissue matrices of articular hyaline cartilage, fibrocartilaginous menisci, and of certain ligaments and tendons are particularly susceptible to pathologic calcification.

• ANKH is clearly implicated in the pathogenesis of familial and idiopathic/sporadic chondrocalcinosis

Diagnosis

• Same as Gout• Positive birefringent• Lab : CBC, ESR, CRP• X-ray for chronic case

Differential diagnosis

• Gout• Septic arthritis• Other crystal arthropathy• Chronic case Rheumatoid arthritis

Treatment

Muscular dystrophy

Introduction

• Progressive muscle weakness• Genetic disease• Effect Dystrophin• Duchenne Muscular dystrophy : Most

common• Becker Muscular dystrophy : Second most

common

Duchene muscular dystrophy

• Most common• Male• 1:3500 live male birth• 1/3 new mutation• 65% family history• Onset : age 3-6 years• Pseudohypertrophy of

calf muscles

Meyeron sign

Diagnosis

• Gait• Gower’s sign• Meyeron sign• Macroglossia• Myocardial

deterioration• IQ ~ 80

• Increase CPK (200x)• Myopathic change

in EMGBx: muscle degeneration

• Immunoblotting: Absence dystrophin

• DNA mutation analysis

Natural history• Progress slowly and

continuously• muscle weakness– lower --> upper

extremities• unable to ambulate:

10 year (7-12)• death from

pulmonary/ cardiac failure: 2-3rd decade

Treatment

• Supportive treatment : Cardiology, Respiratory

• Prednisolone 0.75 mg/Kg/day• Surgery required to stabilize skeletal

structure : Scoliosis• Counseling family for another child • Specific treatment : PTC 124 *, PRO051**