Disclosures I have nothing to disclose. The ABCs of non-neoplastic - - PowerPoint PPT Presentation

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The ABCs of non-neoplastic joint disease: Arthritis, Bacteria and Crystals

Andrew Horvai, MD, PhD Clinical Professor, Pathology

Disclosures

I have nothing to disclose.

Introduction: Joints

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Solid = nonsynovial = synarthroses

• Fibrous: cranial sutures, teeth
• Cartilaginous: Symphysis pubis

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Cavitated = synovial

• Joint space filled with hyaluronic acid-rich fluid
• Covered by synovial membrane
• Synoviocytes (two types), no basement membrane
• Hyaline cartilage
• Water (70%), collagen type 2 (10%), proteoglycans (8%)
• Limited regenerative capacity

Normal infant joint

2 Normal adult joint Normal synovium

Non-neoplastic joint disease

• Noninfectious arthritis
• Osteoarthritis (OA)
• Rheumatoid arthritis (RA)
• Others
• Seronegative spondyloarthropathies
• Juvenile idiopathic arthritis (JIA)
• Crystal induced arthritis
• Gout
• Pseudogout
• Infectious arthritis
• Septic (bacterial) arthritis
• Infected arthroplasty
• Lyme arthritis

Osteoarthritis

• Definition: A degeneration of articular cartilage resulting in

structural and functional failure of synovial joints

• Clinical:
• Most common disease of joints
• Incidence
• Primary (oligoarticular): 40% of people over 70
• Secondary (polyarticular): Rare, underlying disease, younger
• Knee, hip, DIP and PIP joints
• Pathogenesis
• Chondrocyte injury, genetic predisposition, biomechanical
• Cartilage degradation > repair
• Loss of cartilage and chondrocytes
• Despite suffix –itis inflammation is minimal

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Osteoarthritis

Osteoarthritis: duplicated tidemark

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Osteoarthritis: subchondral cyst Osteoarthritis: Schmorl’s node

Rheumatoid arthritis

• Definition: Chronic inflammatory, autoimmune disorder principally

attacking joints producing a nonsuppurative, proliferative and inflammatory arthritis

• Clinical
• Prevalance 1-5%
• Female: Male 3:1
• MCP and PIP, wrist, elbow
• Extraarticular: lung, kidney, soft tissue (rheumatoid nodule)
• Pathogenesis
• Genetics (HLA) + Environmental (infection, smoking)
• TH1 TH17 and B cell responses to self antigens (citrullinated

peptides)

• Lymphocytes, antibodies and immune complex enter joint
• Pannus, destruction of bone and cartilage,

Rheumatoid arthritis

5 Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis

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Rheumatoid nodule Rheumatoid nodule

Horvai A, Robbins Textbook of Pathology, Elsevier, 2015

Arthritis summary

Other non-infectious arthritis

• Seronegative spondyloarthropathies
• Sacroiliac joints
• Pathology best seen in ligamentous attachments (entheses)
• RhFactor-, association with HLA-B27
• Subtypes: Ankylosing spondylitis, reactive arthritis, enteritis

associated arthritis, psoriatic arthritis

• Juvenile idiopathic arthritis
• Heterogeneous group of joint disorders, present before age 16 and

persist for at least 6 weeks

• Oligoarthritis, large joints
• ANA+ RhFactor-

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Ankylosing spondylitis

Enthesopathy of Ankylosing spondylitis

Juvenile idiopathic arthritis

Crystal induced arthritis

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Gout (Calcium urate) arthritis

• Definition: Transient attacks of acute arthritis initiated by urate

crystals within and around joints.

• Clinical:
• Incidence ~ 50 / 100,000
• M>F, renal failure, obesity predispose
• Monoarticular acute arthritis, MTP joint most common
• Asymptomatic intercritical period
• Chronic tophaceous gout
• Pathogenesis
• Hyperuricemia (6.8 mg/dL) necessary but not sufficient
• Most commonly due to reduced excretion of urate
• Age, genetics, EtOH, obesity, thiazide diuretic
• Urate crystals trigger inflammation, leukocyte recruitment

Gout

Acute Gout arthritis (joint aspirate)

Gout (alcohol process)

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Gout (alcohol process) Gout Gout (polarized optics) Pseudogout (calcium pyrophosphate dihydrate, CPPD)

• Definition: Deposition of CPPD crystals in and around joints

causing acute, chronic or subacute arthritis.

• Clinical:
• May be asymptomatic; CPPD crystals may be secondary

degenerative phenomenon in joints and soft tissue

• M=F, >50 years old
• Knees, elbows most commonly affected
• Relapsing course, ~50% chronic joint damage similar to OA
• Pathogenesis
• Not known
• Proteoglycans in articular cartilage normally inhibit mineralization,

their loss may promote CPPD deposits

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Pseudogout Pseudogout

CPPD CPPD

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CPPD (polarized optics)

Infectious arthritis Septic (bacterial) arthritis

• Definition: Pyogenic or granulomatous infection of synovium and articular

surfaces

• Clinical:
• Fever, swollen, erythematous, painful joint
• Synovial fluid grey-green, 20K-200K WBC/µL, >75% PMN
• Compared to osteomyelitis, joint infection is a more urgent problem

because cartilage has limited appear to regenerate

• Pathogenesis
• Inoculation of joint by infectious organisms
• Usually bacterial
• Hematogenous
• Periosteal
• Direct

Septic arthritis

• S. aureus
• S. pyogenes

S. Pneumoniae Gram negative Other

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Septic arthritis Septic (bacterial) arthritis

• Definition: Pyogenic or granulomatous infection of synovium and

articular surfaces

• Orthopedic hardware (joint prostheses) at high risk
• Lyme arthritis
• Infection with Borrelia burgdorferi
• 10% develop arthritis in late stage, large joints (since most

cured)

• Borrelia in joints (~25% by Warthin Starry, ~50% by PCR)

Infectious arthritis Infectious arthritis

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Infectious arthritis Infectious arthritis Granulomatous infectious arthritis

Infected arthroplasty

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Infected arthroplasty

Early Late

Time <3 months > 24 months Organisms

• S. Aureus
• E. Coli

Coag – Staph

• P. Acnes

Route Direct Hematogenous Clinical Fever ↑ WBC Pain Loosening Instability Pain

• The “delayed” form (3-24 months) with overlapping features

between Early and Late.

Hardware loosening

• Aseptic loosening (85%)
• Wear induced particle

debris

• Stress shielding

(atrophy)

• Hardware failure
• Septic loosening

(15%)

• Infection

Immediate replacement Removal Antibiotic cement spacer 6 wks IV antibiotics

Septic loosening

Gold standard: Positive culture from multiple

sites

Intraoperative: Neutrophils in synovium or

granulation tissue or capsule

Criterion Sensitivity Specificity Feldman 5 neutrophils/hpf in > 5 hpf* 25% 98% Athanasou 10 neutrophils/10 hpf 70% 64% *hpf: 400X (0.5 mm2) high power field.

Bori G et al. J Bone Joint Surg 2007 89:1232

Septic loosening

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Septic loosening

PMNs in capsule: YES

PMNs in fibrin: NO

PMNs in vessels: NO

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Other common arthroplasty findings

• Wear debris reaction
• Xanthoma cells
• Capsule (synovial metaplasia)
• Foreign materials

Barium: radio-opaque contrast Methyl methacrylate: cement Polyethylene: articular surface (large prosthesis) Silastin: silicone rubber (small prosthesis) Rosenberg, A. E., et al. (2011). Semin Diagn Pathol 28(1): 65-72.

Wear debris reaction Wear debris reaction Xanthoma cells

17 Barium and Me-Methacrylate

Polyethylene Polyethylene

Lyme disease

Horvai A, Robbins Basic Pathology, Elsevier, 2017.

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Lyme arthritis (images courtesy Dr. M. Klein, HSS)

Take-home messages

• 1. Osteoarthritis, the most common joint disease, usually

lacks inflammation

• 2. Lymphoid follicles with germinal centers is consistent with

rheumatoid arthritis but is seen in other autoimmune arthritides

• 3. Neutrophils in fibrin and vascular lumina do not count for

septic loosening of a prosthesis

• 4. CPPD crystals can occur as a secondary phenomenon in

degenerative joints for various reasons and are not diagnostic of pseudogout