Crystalline Arthritis

Question 1

Pathogenesis of Calcium Pyrophosphate dihydrate cyrstal deposition disease

Answer 1

-Dysregulated chondrocyte differentiation to hypertrophy and inorganic pyrophosphate (PPi) metabolism

Question 2

Autosomal dominant familial CPPD crystal deposition disease

Answer 2

-has been linked in multiple kindreds to certain mutations in ANKH, a gene encoding a PPi transporter

Question 3

What drives cell responses to CPPD cyrstals and CPPD crystal-induced inflammation?

Answer 3

-NLRP3 (cryopyrin) inflammasome activation and consequent caspase-1 activation and interleukin (IL)-1β processing

Question 4

Degenerative arthropathy

Answer 4

• caused by CPPD crystal deposition disease
• often involves joints uncommonly affected by primary osteoarthritis such as the metacarpophalangeal, wrist, and elbow joints

Question 5

Diagnosis of CPPD deposition disease before age 55??

Answer 5

-should prompt differential diagnostic consideration of a primary metabolic or familial disorder, and hyperparathyroidism should always be considered in CPPD deposition disease presenting in patients older than the age of 55

Question 6

Diagnosis of CPPD?

Answer 6

high res ultrasound, radiographic chondrocalcinosis is not detectable in all joints affected by the disease

Question 7

Basic calcium phosphate (BCP) crystal deposition in articular cartilage is linked with?

Answer 7

-osteoarthritis, particularly with osteoarthritis of increased severity

Question 8

BCP crystals

Answer 8

-do not demonstrate birefringence, and specialized methods are required to conclusively identify BCP crystals in specimens from the joint

Question 9

Vast majority of CPPD crystal deposition disease is??

Answer 9

-idiopathic/sporadic, but early-onset familial disease also occurs

Question 10

Gene linked to familial CPPD crystal deposition disease??

Answer 10

ANKH on chromosome 5p

which encodes a transmembrane protein with functions including PPi transport

Question 11

What is susceptible to pathologic calcification?

Answer 11

-loose avascular connective tissue matrices of articular hyaline cartilage, fibrocartilaginous menisci, and of certain ligaments and tendons

Question 12

Joint cartilage pathologic calcification

Answer 12

-reflects complex interplay between organic and inorganic biochemistry of Pi and PPi metabolism, aging, dysregulated chondrocyte growth factor responsiveness and differentiation, and other factors

Question 13

CPPD in the elderly?

Answer 13

• can mimic conditions including gout, infectious arthritis, primary osteoarthritis, RA, or polymyalgia rheumatica
• It can also present as fever of unknown origin

Question 14

Pseudogout

Answer 14

• major cause of acute monoarticular or oligoarticular arthritis in the elderly
• attacks typically involve a large joint, most often the knee, and less often the wrist or ankle, and, unlike gout, rarely the first metatarsophalangeal joint

Question 15

Chronic degenerative arthropathy in CPPD deposition disease

Answer 15

-commonly affects certain joints that are typically spared in primary OA (e.g., metacarpophalangeal joints, wrists, elbows, glenohumeral joints)

Question 16

Acute Synovitis

Answer 16

rare in HA crystal depssition

Question 17

Basic Calcium Phosphate Crystal Disease Clinical Features

Answer 17

HA crystal in in bursae, tendons, ligaments, and soft tissues of young women - cause inflammatory syndromes including subacromial bursitis and a form of pseudopodagra
-patients with advanced chronic renal failure (dialysis) may develop symptomatic articular and periarticular BCP crystal deposition, which may be destructive and involve the axial skeleton. They may resemble or be associated with CPPD deposition disease

Question 18

CALCIUM CRYSTAL DISEASE: DIAGNOSIS AND DIAGNOSTIC TESTS

Answer 18

• Presence of radiographic evidence for chondrocalcinosis is a common finding in the aged and does not indicate that the patient’s symptomatic articular problem is due to CPPD deposition disease, which is often asymptomatic
• compensated polarized light microscopy is essential to confirm the presence of positively birefringent CPPD crystals, though it should be noted that some CPPD crystals are nonbirefringent
• Patients with arthritis in whom CPPD deposition disease is part of the differential diagnosis can be screened by plain radiographs, but high-resolution ultrasound of the affected joint is a useful and sensitive alternative approach

Question 19

CALCIUM CRYSTAL DISEASE: TREATMENT

Answer 19

• CPPD deposition disease treatment involves alleviation and prophylaxis of acute arthritic attacks, but therapy to lessen chronic and anatomically progressive sequelae of crystal deposition is not well developed for CPPD disease.
• pseudogout treatment is similar to that for acute gout