CRYSTAL ASSOCIATED DISEASE 11/7/20151Dr. Alka Stoelinga.

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CRYSTAL ASSOCIATED DISEASE 11/7/20151Dr. Alka Stoelinga

Calcium pyrophosphate dihydrate (CPPD) deposition PSEUDOGOUT 11/7/20152Dr. Alka Stoelinga

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 arthropathy is a term that may refer to either of the above. Statistically, the knee joint is the most commonly affected 11/7/20153Dr. Alka Stoelinga

11/7/2015Dr. Alka Stoelinga4 PP1 Protein phosphatase 1 NPP1 nucleotide pyrophosphatases TNAP tissue-nonspecific alkaline phosphatase

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. 11/7/2015Dr. Alka Stoelinga5

ASSOCIATIONS OF CPPD DEPOSITION 1.AGEING Most common with age >55 2.OSTEOARTHRITIS, JOINT PAIN Common Knee (Hyaline cartilage and menisci)  Most prevalent site Wrist (Triangular fibrocartilage) Pelvis (Symphysis pubis) 3.FAMILIAL PREDISPOSITION Rare but + 4.METABOLIC DISEASE Rare Hemochromatosis Hyperparathyroidism Hypophosphatasia Hypomagnesemia Wilson’s disease 11/7/2015Dr. Alka Stoelinga6

The symptoms of CPPD crystal deposition disease are caused by two processes: 1.the presence of tiny CPPD crystals in the joints and 2.the body's reaction to these crystals. 11/7/2015Dr. Alka Stoelinga7

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 11/7/2015Dr. Alka Stoelinga8

Clinical features Chronic (Pyrophosphate) arthritis – Mostly elderly female – Most common site: Knee F/B Wrist, shoulder, elbow, hips and midtarsals Hand  2 nd and 3 rd 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 11/7/2015Dr. Alka Stoelinga9

Investigations 1.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 2.Radiographs – Chondrocalcinosis in hyaline and fibrocartilage (Occasionally capsule or ligament) with/ without structural changes of osteoarthritis 3.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 11/7/2015Dr. Alka Stoelinga10

Classic radiographic features of CPPD Chondrocalcinosis Degenerative change without apparent osteophytosis 11/7/2015Dr. Alka Stoelinga11

11/7/2015Dr. Alka Stoelinga12 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

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). 11/7/2015Dr. Alka Stoelinga13

11/7/2015Dr. Alka Stoelinga14

Treatment Aspiration of synovial fluid Florid pseudogout – Intraarticular steroid injection NSAIDS and Colchicine (Avoid in very elderly patients) Early mobilization 11/7/2015Dr. Alka Stoelinga15

11/7/2015Dr. Alka Stoelinga16

Osteoarthritis Osteoarthritis (OA) also known as degenerative arthritis or degenerative joint disease Unlike RA, It is not an inflammatory joint disease Osteoarthritis can be defined as a painful condition of synovial joints characterized by: 1.Focal loss of articular hyaline cartilage 2.Simultaneous proliferation of new bone with remodeling of joint contour 11/7/2015Dr. Alka Stoelinga17

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. 11/7/2015Dr. Alka Stoelinga18

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 11/7/2015Dr. Alka Stoelinga19

Young onset osteoarthritis: Causes 1. Monoarticular Previous trauma, localized instability 2. Polyarticular/ Pauciarticular Prior joint disease (Juvenile idiopathic arthritis) Metabolic or endocrine disease Spondylo-epiphyseal dysplasia Late avascular necrosis Neuropathic join Endemic Osteoarthritis 11/7/2015Dr. Alka Stoelinga20

11/7/2015Dr. Alka Stoelinga21 Common Sites

11/7/2015Dr. Alka Stoelinga22

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. 11/7/2015Dr. Alka Stoelinga23

11/7/2015Dr. Alka Stoelinga24 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)

11/7/2015Dr. Alka Stoelinga25 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

Clinical features PAIN Patient over 45years of age (Often >60) Insidious onset over months or years Variable or intermittent over time (Good days, bad days) Mainly related to movement, weight bearing; relieved by rest Only brief (<15 mins) morning stiffness and brief (<1 min) gelling after rest Usually only 1 or few painful joints (Not multiple regional pain) CLINICAL SIGNS Restricted movement (Capsular thickening, blocking by osteophytes) Palpable, sometimes audible, crepitus (Rough articular surfaces) Bony swelling (Osteophytes) around joint margins Deformity, usually without stability Joint line or periarticular tenderness Muscle wasting or weakness No or only mild synovitis (effusion, increasing warmth) 11/7/2015Dr. Alka Stoelinga26

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. 11/7/2015Dr. Alka Stoelinga27

11/7/2015Dr. Alka Stoelinga28 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)

11/7/2015Dr. Alka Stoelinga29

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 11/7/2015Dr. Alka Stoelinga30

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 11/7/2015Dr. Alka Stoelinga31

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) 11/7/2015Dr. Alka Stoelinga32