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

CRYSTAL ASSOCIATED DISEASE

04/20/23 1Dr. Alka Stoelinga

Calcium pyrophosphate dihydrate (CPPD) depositionPSEUDOGOUT

04/20/23 2Dr. Alka Stoelinga

CPDDCalcium 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 affected04/20/23 3Dr. Alka Stoelinga

04/20/23 Dr. Alka Stoelinga 4

PP1 Protein phosphatase 1NPP1 nucleotide pyrophosphatasesTNAP 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.


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


• The symptoms of CPPD crystal deposition disease are caused by two processes: 1. the presence of tiny CPPD crystals in the joints

and2. the body's reaction to these crystals.


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


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


Investigations1. 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


Classic radiographic features of CPPD

• Chondrocalcinosis • Degenerative change without apparent

osteophytosis



• 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).



Treatment

• Aspiration of synovial fluid• Florid pseudogout

– Intraarticular steroid injection

• NSAIDS and Colchicine (Avoid in very elderly patients)

• Early mobilization



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 cartilage2. Simultaneous proliferation of new bone with

remodeling of joint contour04/20/23 Dr. Alka Stoelinga 17

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.


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


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



Common Sites


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.



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)


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)


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.



Osteophytes on the fingers or toes are known as Heberden's nodes (if on the DIP joint) orBouchard's nodes (if on the PIP joints)


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


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


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)


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