Pathology · Year 2 · from Pathology

Case 1: Rheumatoid Arthritis - Chronic Mononuclear Inflammation

Patient Demographics

• Age: 42 years old
• Sex: Female
• Occupation: Office administrator

Chief Complaint

"My hands are stiff and painful every morning for the past 6 months"

History of Present Illness

A 42-year-old woman presents with a 6-month history of bilateral hand pain, stiffness, and swelling. The stiffness is worst in the morning and lasts over 2 hours before improving with activity. She has noted symmetric involvement of her metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints bilaterally. She also reports fatigue, low-grade fevers, and a 5-pound unintentional weight loss. The symptoms have progressively worsened, and she now has difficulty gripping objects and buttoning her clothes. Her mother had similar joint problems and developed hand deformities.

Physical Examination

• Vital Signs: BP 118/72 mmHg, HR 76 bpm, Temp 37.2°C (99.0°F)
• General: Well-appearing woman with obvious hand deformities
• Hands:
• Symmetric swelling of MCP and PIP joints bilaterally
• Warmth and tenderness at involved joints
• Early ulnar deviation at MCP joints
• No DIP involvement (spares distal joints)
• Wrists: Bilateral synovial thickening and tenderness
• Elbows: Small subcutaneous nodules on extensor surface
• Other joints: Mild swelling of bilateral knees

Diagnostic Workup

Laboratory Studies:

Imaging:

• X-ray hands: Periarticular osteopenia, joint space narrowing, early marginal erosions at MCP joints, soft tissue swelling

Synovial Fluid Analysis (right knee):

Synovial Biopsy Histopathology:

• Marked synovial hyperplasia with villous hypertrophy
• Dense infiltration by lymphocytes and plasma cells
• Germinal center formation within synovium
• Pannus tissue eroding into articular cartilage
• Increased vascularity

Pathology Correlation

This case demonstrates the features of chronic mononuclear inflammation:

1. Chronic Inflammation Characteristics:

• Mononuclear cell infiltrate (lymphocytes, plasma cells, macrophages)
• Prolonged duration (months to years)
• Simultaneous tissue destruction and repair
• Fibrosis and angiogenesis

1. Cellular Players:

• Macrophages: M1 phenotype producing TNF-alpha, IL-1, IL-6
• T lymphocytes: CD4+ Th1 and Th17 cells driving inflammation
• B lymphocytes and plasma cells: Producing RF and anti-CCP antibodies
• Fibroblast-like synoviocytes: Form proliferating pannus

1. Pannus Formation:

• Granulation tissue-like mass on articular surface
• Contains activated fibroblasts, inflammatory cells, new vessels
• Secretes matrix metalloproteinases (MMPs) that degrade cartilage
• Produces receptor activator of NF-kappaB ligand (RANKL) promoting osteoclast activation

1. Rheumatoid Nodule:

• Central zone of fibrinoid necrosis
• Palisading macrophages around necrotic center
• Outer zone of granulation tissue

Clinical Image

Clinical photograph of rheumatoid arthritis showing characteristic hand involvement with symmetric swelling of the MCP and PIP joints, ulnar deviation of the fingers, and swan-neck deformities. These changes result from chronic synovial inflammation with pannus formation eroding cartilage and bone.

Image Source: Wikimedia Commons - "Rheumatoid Arthritis" License: CC BY-SA 3.0 URL: https://commons.wikimedia.org/wiki/File:Rheumatoid_Arthritis.JPG

Diagnosis

Rheumatoid Arthritis - Seropositive (RF+, anti-CCP+) with erosive disease

Treatment

1. Methotrexate (disease-modifying antirheumatic drug - DMARD)
2. Folic acid supplementation
3. NSAIDs for symptomatic relief
4. Short course of low-dose prednisone for bridging
5. Physical therapy and occupational therapy
6. Consideration of biologic therapy (anti-TNF) if inadequate response

Teaching Points

1. Chronic inflammation is characterized by mononuclear cell infiltration, tissue destruction, and fibrosis occurring simultaneously
2. Pannus represents aberrant granulation tissue that destroys cartilage and bone
3. Rheumatoid factor and anti-CCP antibodies are produced by plasma cells infiltrating the synovium
4. The anemia of chronic disease reflects cytokine effects on iron metabolism (hepcidin elevation)
5. Symmetry of joint involvement is characteristic of RA and helps distinguish from other arthritides
6. DIP sparing helps distinguish RA from osteoarthritis and psoriatic arthritis
7. Anti-TNF therapies target the key cytokine driving chronic synovial inflammation

All cases for this lecture as Markdown