Arthritis and Rheumatic Diseases

• Lecture topic is joint pathology, presented on March 19, 2024, by Jasmine Figueroa-Diaz, MD, from the Department of Pathology at Ponce Health Sciences University.

Objectives

• Classification and structure of synovial joints will be covered.
• Pathogenesis and morphology of osteoarthritis, rheumatoid arthritis (RA), gout, and pseudogout will be discussed.
• Tumors and tumor-like conditions of joints are on the agenda.

Joints: The Basics

• Joints/articulations are where bones meet, allowing for movement and providing mechanical stability.
• Joints can either be solid (non-synovial) or cavitated (synovial).

Types of Joints

• Synarthrosis offers minimal movement and ensures structural integrity, made up of fibrous tissue or cartilage, found in the cranium, roots of teeth, jawbones, manubrium-sternalis, and pubic symphysis.
• Synovial joints allow a wide range of motion, featuring a dense capsule, ligaments, and muscles.

Synovial Joint Components

• Key components is the synovial membrane.
• Hyaline cartilage acts as a shock absorber, water-resistant surface consisting of collagen type II, water, proteoglycans, and chondrocytes.
• Hyaluronic acid functions as a lubricant in the joint.
• Tendons and muscles are also crucial parts.

Cytokines

• Cytokines are an important mechanism in many joint diseases.
• IL-1 and TNF trigger the degradative process.
• Sources of cytokines include chondrocytes, synoviocytes, fibroblasts, and inflammatory cells.
• Cytokines contribute to the destruction of articular cartilage by indigenous cells.

Joint Pathology: An Overview

• Joint pathologies include various forms of arthritis and tumor-like lesions.
• Types of arthritis include osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, seronegative spondyloarthropathies (such as ankylosing spondyloarthropathy, Reiter syndrome, enteritis-associated arthritis, and psoriatic arthritis), infectious arthritis, and crystal-induced arthritis.
• Tumor and tumor-like lesions of joints include cysts (ganglion and synovial cysts) and tenosynovial giant-cell tumors.

Osteoarthritis

• Osteoarthritis is a common disabling condition characterized by progressive erosion of articular cartilage.
• The pathogenesis is multifactorial, involving both genetic and environmental factors like aging and mechanical stress.
• Environmental factors include obesity, muscle strength, joint instability, and alignment, as well as predisposing conditions like congenital developmental deformity, diabetes, and hemochromatosis.
• Chondrocytes secrete collagen type II and matrix components.
• Decreased collagen synthesis, increased breakdown, and eventual chondrocyte death are the key features.

Osteoarthritis (OA): Stages

• Osteoarthritis development involves chondrocyte injury.
• Early phase involves chondrocyte proliferation and secretion of inflammatory mediators, leading to increased water content, decreased proteoglycans, matrix cracking, and remodeling.
• Late phase encompasses repetitive injury and subsequent chronic inflammation.
• Cartilage sloughs off and sclerosis of underlying bone occurs.
• Exposed bone smoothens, and osteophytes develop.

Macroscopic and Radiographic Findings in Osteoarthritis

• Eburnation and osteophyte formation are evident
• Osteophyte
• Sclerosis

Osteoarthritis symptoms

• Morning stiffness is present, typically lasting less than 30 minutes.
• Pain worsens with use.
• Hips, lower lumbar spine, knees, distal and proximal interphalangeal joints (DIP and PIP) are common areas affected.
• Heberden nodes (in DIP) indicate osteophyte formation.

Rheumatoid Arthritis (RA)

• RA is a chronic, systemic inflammatory disorder, affecting the skin, blood vessels, heart, lung, and muscle.
• The joints exhibit synovitis, granulation tissue (pannus) formation, cartilage destruction, and ankylosing (fusion).
• RA is an autoimmune disorder appearing in genetically susceptible individuals with the HLA-DR4.
• Pathogenesis is related to activation of CD4+ T helper cells.
• More common in women aged 40-70 years old.

Rheumatoid arthritis: pathogenesis

• Genetic susceptibility includes the HLADRB1
• HLADRB1 provides a Specific binding site of arthritogenic factor
• Environmental factors which initiate disease: EBV, retrovirus, parvovirus, mycobacteria, Borrelia, Proteus mirabilis, and Mycoplasma
• 80% of individuals have autoantibodies to Fc portion of autologous IgG.
• Rheumatoid factor: IgM against RA-IgG
• Autoimmunity; antibodies to citrulline-modified peptides; Anti-cyclic citrullinated peptide (CCP) antibodies

Rheumatoid Arthritis: Histology

• Synovial inflammatory cells like B cells, CD4+ T cells, plasma cells, and macrophages are present.
• Blood vessels increase in number.
• Fibrin (rice bodies) and PMNs are found on the synovial fluid
• Osteoclasts become active, and pannus forms.

Rheumatoid Arthritis Symptoms

• Rheumatoid nodules appear on the skin.
• Vasculitis occurs in blood vessels.
• Felty's syndrome manifests as RA plus splenomegaly and neutropenia.
• Caplan syndrome consists of rheumatoid nodules in the lung and pneumoconiosis.
• The Morning stiffness improves with activity.
• Arthritis affects three or more joints, including the hand joints (PIP), elbows, ankles, and knees.
• Symmetrical; small joints are affected before larger ones
• Fever, malaise, weight loss, and myalgias develop.
• Serum rheumatoid factor is present

Clinical course of Rheumatoid Arthritis

• Radiological hallmarks include joint effusions and Juxta-articular osteopenia with erosions.
• Radiological hallmarks include narrowing of the joint space and loss of articular cartilage.
• Treatment involves corticosteroids, methotrexate, and TNF antagonists.

Juvenile Idiopathic Arthritis

• Juvenile idiopathic arthritis is juvenile rheumatoid arthritis affecting children under 16 years, and less than 10% develop serious complications
• This is one of the most common connective tissue diseases
• Can be oligoarticular (<5) joint involvement, polyarticular, or systemic.
• Juvenile idiopathic arthritis Differs with RA in because oligoarthritis is more common, systemic onset is more frequent, large joints are affected, there is no rheumatoid nodules or RF, and ANA +

Juvenile Idiopathic Arthritis: Classification

• Systemic arthritis involves Abrupt onset, remitting, high fevers, migratory and transient rash, hepatosplenomegaly, and serositis, and recurrent flares
• Oligoarthritis affects less than 5 joints during the first 6 months of disease; absence of psoriasis and HLA-B27
• RF-negative polyarthritis involves greater than 5 joints during the first 6 months of disease.
• With RF-negative polyarthritis, stiffness and contraction occurbut little swelling.
• Enthesitis-related arthritis mainly affects male children younger than 6 years and with HLA-B27 positive
• Other types include psoriatic arthritis and undifferentiated arthritis.

Seronegative Spondyloarthropathies

• Seronegative Spondyloarthropathies conditions include Ankylosing spondylitis, Reiter syndrome, Enteritis-associated arthritis, and Psoriatic arthritis
• These have No specific autoantibodies, hence the name seronegative.

Ankylosing Spondyloarthritis

• Ankylosing Spondyloarthritis other names: Rheumatoid spondylitis or Marie-Strumpell disease
• Axial joints sacroiliac have greater impact than lower back pain
• Mostly seen in men (2nd to 3rd decade)
• 90% HLA-B27 positive
• Other genes: ARST1 and IL23R
• Spinal immobility
• Complications: fractured spine, uveitis, aortitis, and amyloidosis

Reiter Syndrome

• Present with Conjunctivitis reactive arthritis,Nongonococcal urethritis or cervicitis.
• Reiter Syndrome can lead to sausage finger,balanitis, and cardiac conduction abnormalities.
• Primarily > men in 20's-30s
• HLA-B27
• autoimmune reaction initiated by prior infection of; GIT (Shigella, Salmonella, Yersinia, Campylobacter)
• Episodes may wax and wane; 50% recur
• May be the first manifestation of HIV

Enteritis-Associated Arthritis

• Enteritis-Associated Arthritis is associated with gastrointestinal tract infection.
• This can be Yersinia, Salmonella, Shigella, Campylobacter
• Cell membranes of these organisms have lipopolysaccharides which is
• Knees and ankles commonly affected

Psoriatic Arthritis

• Susceptibility to Psoriatic Arthritis is genetically determined
• Related to the HLA-B27 and HLA-Cw6 30-50 years
• Distal interphalangeal joints of hands and feet are 1st involved
• Sausage-like finger with pitted nails
• Joint destruction is less frequent

Hand joints affected by rheumatologic diseases

• DIP: Psoriatic arthritis and Osteoarthritis (Heberden's nodes)
• PIP: Osteoarthritis (Bouchard's nodes), Rheumatoid arthritis, SLE
• MCP: Rheumatoid arthritis, SLE, and Hemochromatosis

Infectious Arthritis

• Suppurative arthritis can be Gonococcus, Staph, Strep, H. influenzae, G-bacilli, and Salmonella.
• H. influenza (children < 2y)
• S. aureus (older children and adults)
• Can be due to tuberculous arthritis
• Can be Virally induced by Parvovirus B19, Rubella, EBV Hepatitis B and C viruses, and HIV

Lyme arthritis

• Lyme arthritis is caused by Borrelia burgdorferi
• Ixodes ricinus complex
• 60-80% of untreated individuals develop joint symptoms within a few weeks to 2 yrs after onset of disease
• Remitting and migratory arthritis
• Pathogenesis: HLA-DR molecules binds to bacterial outer surface protein A

Crystal-Induced Arthritis

• Gout and Gouty Arthritis, Pseudo-Gout

Classification of Gout

• 1° Gout (90% of cases) is due to excessive uric acid production.
• This is the end product of purine metabolism
• It can be prompted by diet, enzyme defects (either known or unknown)
• Reduced excretion of uric acid with normal production
• 2° Gout is due to overproduction of uric acid with increased urinary excretion, and it's (10% of cases)
• This has Increased nucleic acid turnover or inborn errors of metabolism
• It can be due to Reduced excretion of uric acid with normal production or as a Chronic renal disease

Gouty arthritis

• Can cause transient attacks of acute arthritis or nephropathy
• Articular crystal can deposit secondary to hyperuricemia > 6.8 mg/dL
• Develop tophi, forming a mass of urates
• Factors that can contribute to the change of asymptomatic hyperuricemia which can lead to 1° gout; Age/ duration of hyperuricemia; genetic predisposition; heavy alcohol consumption; certain drugs or from lead toxicity.

Tophi: pathognomonic hallmark

Clinical Course: Stages of Gout

• Composed of asymptomatic hyperuricemia, acute gouty arthritis, asymptomatic period, and/or chronic tophaceous gout.
• Asymptomatic hyperuricemia appears at puberty in males and after menopause in females
• In Acute gouty arthritis the first attacks are mono-articular and severe
• Descending order of frequency: Insteps, ankles, heels, knees, wrists, fingers, and elbows
• 20% of patients with chronic gout die of renal failure

Management of Gout

• Utilize both nonpharmacologic and pharmacologic modalities tailored to risk factors.
• Stress patient education and lifestyle changes (weight loss and alcohol reduction).
• Address patient's comorbidities like hypertension, hyperglycemia, hyperlipidemia, obesity, and smoking. Oral colchicine and/or NSAIDs are first-line agents for systemic treatment of acute attacks.
• Low doses of colchicine may be sufficient for some patients with acute gout (higher doses may cause side effects). Intra-articular aspiration and injection of a long-acting steroid are safe and effective for acute gout attacks.
• Prophylaxis against acute attacks during the first months of urate-lowering therapy includes colchicine and/or NSAIDs.
• Gout associated with diuretic therapy: stop diuretic therapy and use losartan and fenofibrate with hypertension and hyperlipidemia.

Pharmacotherapy for Acute Gout Attacks

• Use NSAIDs for elderly patients, those with renal insufficiency heart failure, peptic ulcerations from liver disease, and concurrent anticoagulants
• Use Corticosteroids and avoid if patient has septic joints. Use with caution in pts w. diabetes
• Colchicine shoulf be avoided in if pt.has severe renal or hepatic impairment
• Use within first 24 hours of the attack
• Reduce dosage in older patients, however, diarrhea limit its use
• Avoid IV preparation

Pseudo gout

• Primarily from Calcium Pyrophosphate Crystal Deposition (CPPD) or chondrocalcinosis
• Often see in pts. >50 years
• Equal rates for Females and Males.
• Hereditary: Autosomal Dominant from with the ANKH gene (transmembrane pyrophosphate transport channel)
• Secondary from Hyperparathyroidism, Hemochromatosis, Hypomagnesemia, Hypothyroidism, Ochronosis, Diabetes
• Crystal deposition in articular matrix, menisci, and intervertebral discs
• Present with acute and subacute or chronic arthritis and can be monoarticular or polyarticular with in the Knees, wrist, elbows, shoulders and ankles.

Joint Tumor-Like Lesions

• Include Ganglion and synovial cysts
• Ganglion cysts are small 1-1.5 cm, near joint capsule, and wrist.
• Synovial cysts involve Herniation of synovium through joint capsule or massive enlargement of bursa and can result in Baker cyst

Joint Tumor-Like lesions: Tenosynovial giant-cell tumors

• Have Chromosomal translocation: t(1;2)(p13;q37) causing Pigmented villonodular synovitis
• 20-40 yrs
• Treatment: Surgery

Questions cover synovial joints, osteoarthritis, rheumatoid arthritis, gout, pseudogout, juvenile idiopathic arthritis, seronegative spondyloarthropathies, ankylosing spondylitis, and reactive arthritis. It assesses understanding of the characteristics, pathology, and genetic markers associated with these conditions.