CRYSTAL ASSOCIATED DISEASE

1. CRYSTAL ASSOCIATED DISEASE Dr. Alka Stoelinga

2. Calcium pyrophosphate dihydrate (CPPD) depositionPSEUDOGOUT Dr. Alka Stoelinga

3. CPDD • Calcium pyrophosphate deposition disease (CPDD) is a metabolic arthropathy caused by the deposition of calcium pyrophosphate dihydrate (CPPD) in and around joints, especially in hyaline and fibrocartilage of joints • CPDD is often asymptomatic, with only radiographic changes (i.e., chondrocalcinosis), various clinical manifestations may occur, • Including acute (pseudogout) and chronic arthritis. • Pseudogout refers to the acute symptoms of joint inflammation or synovitis: • Red, tender, and swollen joints that may resemble gouty arthritis • Chondrocalcinosis, refers to the radiographic evidence of calcification in hyaline and/or fibrocartilage. • Pyrophosphate arthropathyis a term that may refer to either of the above. • Statistically, the knee joint is the most commonly affected Dr. Alka Stoelinga

4. PP1 Protein phosphatase 1 NPP1 nucleotide pyrophosphatases TNAP tissue-nonspecific alkaline phosphatase Dr. Alka Stoelinga

5. Etiology • Aged and normal fibrocartilage and hyaline cartilage of knee joints and some other joints • Strong association with osteoarthritis • Factors increasing CPPD deposition are: • Reduction in concentration of proteoglycan and other natural inhibitors of crystal formation • Increased extracellular pyrophosphate levels due to upregulated chondrocyte metabolism (Increased breakdown of adenosine triphosphate results in increased pyrophosphate levels in joints) • Genetic association: • Autosomal dominant pattern • Gene ANKH and chromosome 8q is involved in crystal-related inflammatory reactions and inorganic phosphate transport. • Excessive calcium (due to hypomagnesemia) has a potential relationship with chondrocalcinosis, and magnesium supplementation may reduce or alleviate symptoms. Dr. Alka Stoelinga

6. Dr. Alka Stoelinga

7. The symptoms of CPPD crystal deposition disease are caused by two processes: • the presence of tiny CPPD crystals in the joints and • the body's reaction to these crystals. Dr. Alka Stoelinga

8. Clinical features • Acute synovitis (Pseudogout) • Most common cause of acute monoarthritis in elderly • Most common site: • Knee • F/B Wrist, shoulder, ankle and elbow • Triggering factors: • Direct trauma • Intercurrent illness/ Any surgery • Typical attack: • Resembles gout • Rapidly developing • Severe pain, stiffness and swelling within 6-24hrs • Overlying erythema • Examination: • Very tender joint, held in ‘loose pack’ position • Signs of marked synovitis • Large/ tense effusion, warmth, restricted movement and stress pain • Fever, confusion, ill looking Dr. Alka Stoelinga

9. Clinical features • Chronic (Pyrophosphate) arthritis • Mostly elderly female • Most common site: • Knee • F/B Wrist, shoulder, elbow, hips and midtarsals • Hand 2nd and 3rd metacarpophalangeal joints are most commonly affected • Typical symptoms: • Chronic pain • Variable early morning and inactivity stiffness • Functional impairment • Acute attacks may superimpose in chronic h/o pain • Examination: • Features of osteoarthritis (Bony swelling, crepitus, restriction) • Synovitis • Wrist involvement Carpal tunnel syndrome • Large/ tense effusion, warmth, restricted movement and stress pain • Heberden’s nodes Dr. Alka Stoelinga

10. Investigations • Synovial fluid examination • CPPD crystals (Compensated polarised microscopy) • In pseudogout, CPP crystals appear shorter and often rhomboidal. • Positive birefringent • In gout, crystals of MSU appear as needle-shaped intracellular and extracellular crystals. When examined with a polarizing filter, they are yellow when aligned parallel to the axis of the red compensator, but they turn blue when aligned across the direction of polarization (ie, they exhibit negative birefringence) • Turbid fluid • Blood stained • Radiographs • Chondrocalcinosis in hyaline and fibrocartilage (Occasionally capsule or ligament) with/ without structural changes of osteoarthritis • Metabolic screening • For patients with • Early-onset CPPD deposition; <55yrs • Florid polyarticular chondrocalcinosis • Recurrent acute attacks without chronic arthropathy • Additional clinical/ radiographic features of predisposing disease • Tests to send: • Calcium, Alkaline phosphatase, Magnesium, Ferritin • LFTs Dr. Alka Stoelinga

11. Classic radiographic features of CPPD • Chondrocalcinosis • Degenerative change without apparent osteophytosis Dr. Alka Stoelinga

12. Fig. Frontal radiograph of the wrist shows calcifications of the lunotriquetral ligament (arrowhead) and triangular fibrocartilage (red arrow). Joint space narrowing with sclerosis of the trapezioscaphoid and carpometacarpal joints (yellow arrows) are noted. Note absence of osteophytes.This patient presents with classic radiographic features of CPPD, which include: • Chondrocalcinosis • Degenerative change without apparent osteophytosis Dr. Alka Stoelinga

13. Findings under a light microscope and a polarizing microscope (A1, A2, A3, A4, B1, B2, B3, B4, 250 ; C1, C2, C3, 100 ). Sections stained with H&E demonstrated relevant histopathology (A1, B1, C1); however, they did not show any birefringent crystals under a polarizing microscope (A2, B2, C2). Sections stained with NAES method demonstrated birefringent crystals under polarized light in pseudogout (A4) and gout (B4) but did not show any birefringent crystals in tumoral calcinosis (C4). Dr. Alka Stoelinga

14. Dr. Alka Stoelinga

15. Treatment • Aspiration of synovial fluid • Florid pseudogout • Intraarticular steroid injection • NSAIDS and Colchicine (Avoid in very elderly patients) • Early mobilization Dr. Alka Stoelinga

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17. Osteoarthritis • Osteoarthritis (OA) also known as degenerative arthritis or degenerative joint disease • Unlike RA, It is not an inflammatory joint disease • Osteoarthritiscan be defined as a painful condition of synovial joints characterized by: • Focal loss of articular hyaline cartilage • Simultaneous proliferation of new bone with remodeling of joint contour Dr. Alka Stoelinga

18. Primary Osteoarthritis • Chronic degenerative disorder related to but not caused by aging • As a person ages, the water content of the cartilage decreases as a result of a reduced proteoglycan content • Thus causing the cartilage to be less resilient. • Without the protective effects of the proteoglycans, the collagen fibers of the cartilage can become susceptible to degradation and thus exacerbate the degeneration. • Inflammation of the surrounding joint capsule can also occur, though often mild (compared to that which occurs in rheumatoid arthritis). • This can happen as breakdown products from the cartilage are released into the synovial space, and the cells lining the joint attempt to remove them. • New bone outgrowths, called "spurs" or osteophytes, can form on the margins of the joints • These bone changes, together with the inflammation, can be both painful and debilitating. • Greater prevalence of the disease between siblings and especially identical twins • Up to 60% of OA cases -genetic factors. • TYPES: • Primary generalized nodal OA • Erosive OA (EOA. also called inflammatory OA • EOA is a much less common, and more aggressive inflammatory form of OA which often affects the DIPs and has characteristic changes on X-Ray. Dr. Alka Stoelinga

19. Secondary osteoarthritis Caused by other underlying factors like: • Congenital disorders of joints • Diabetes • Inflammatory diseases (such as Perthes' disease), (Lyme disease), and all chronic forms of arthritis (e.g. costochondritis, gout, and rheumatoid arthritis). • Injury to joints, as a result of an accident or orthodontic operations. • Septic arthritis (infection of a joint ) • Ligamentous deterioration or instability may be a factor. • Marfan syndrome • Obesity • Alkaptonuria • Hemochromatosis • Wilson's disease Dr. Alka Stoelinga

20. Young onset osteoarthritis: Causes Dr. Alka Stoelinga

21. Common Sites Dr. Alka Stoelinga

22. Dr. Alka Stoelinga

23. Clinical features • Common sites: • Most commonly affected joint: Knee • Second most common: Base of thumb • Any joint in the body can be affected :hands, feet, spine, large weight bearing joints, such as the hips and knees • Pain • Causing loss of ability and often stiffness. • Crackling noise (called "crepitus") when the affected joint is moved or touched • Muscle spasm and contractions in the tendons. • As OA progresses • the affected joints appear larger • more stiff and painful • usually feel worse, the more they are used throughout the day • In smaller joints, such as at the fingers, hard bony enlargements, called • Heberden's nodes (on the distal interphalangeal joints) and/or • Bouchard's nodes (on the proximal interphalangeal joints • OA at the toes leads to the formation of bunions • Red or swollen. Dr. Alka Stoelinga

24. Osteophytes on the fingers or toes are known as Heberden's nodes (if on the DIP joint) or Bouchard's nodes (if on the PIP joints) Dr. Alka Stoelinga

25. A bunion is an enlargement of bone or tissue around the joint at the base of the big toe (metatarsophalangeal joint).The big toe (hallux) may turn in toward the second toe (angulation), and the tissues surrounding the joint may be swollen and tender Dr. Alka Stoelinga

26. Clinical features Dr. Alka Stoelinga

27. Diagnosis Osteoarthritis • Diagnosis is made with reasonable certainty based on history and clinical examination • X-rays may confirm the diagnosis. • The typical changes seen on X-ray include: • joint space narrowing • subchondral sclerosis (increased bony formation around the joint) • Subchondral cyst formation and • Osteophytes • Usually other imaging techniques are not necessary to clinically diagnose osteoarthritis. Dr. Alka Stoelinga

28. Osteophytes on the fingers or toes are known as Heberden's nodes (if on the DIP joint) or Bouchard's nodes (if on the PIP joints) Dr. Alka Stoelinga

29. Dr. Alka Stoelinga

30. Treatment • Lifestyle modification (such as weight loss and exercise) and analgesics are the mainstay of treatment Lifestyle modification • Exercise • For most people with OA, graded exercise should be the mainstay of their self-management. • Moderate exercise leads to improved functioning and decreased pain in people with osteoarthritis of the knee • Education • For overweight people • weight loss • Patient education in • The fact that established structural changes are permanent but pain and function can improve • Discuss prognosis of disease: • Good for hand osteoarthritis • More optimistic for knee than hip • Self-management of arthritis • It decreases pain, improves function, reduces stiffness and fatigue, and reduces medical usage Dr. Alka Stoelinga

31. Treatment MEDICAL • Analgesics • Acetaminophen is the first line treatment for OA • Non-steroidal anti-inflammatory drugs (NSAID) • Ibuprofen, COX-2 selective inhibitors (such as celecoxib) • Topical- diclofenac • Opioid analgesics • Morphine and fentanyl • Not routinely be used • Oral steroids • Not recommended in the treatment of OA because of their modest benefit and high rate of adverse effects. • Injection of Glucocorticoids (such as hydrocortisone) leads to short term pain relief that may last between a few weeks and a few months • Tanezumab • Monoclonal antibody that binds and inhibits nerve growth factor • Is thought to relieve joint pain enough to improve function in people with osteoarthritis of the knee • The FDA is reviewing the safety of tanezumab that could still emerge as an effective treatment for the pain of osteoarthritis Dr. Alka Stoelinga

32. Treatment Surgery • If all other measures are ineffective • Joint replacement surgery or • Resurfacing may be required in advanced cases. • Selecting patients for joint replacement • Severe pain (Walking limited to 10 min, severe rest/ night pain) • Age (Old age; Life span of a Prosthesis ~ 15 years) Dr. Alka Stoelinga