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A 68-year-old man comes to the office due to difficulty performing normal day-to-day activities with his hands.  He has had pain in his finger joints, wrists, and knees for many years and has been taking over-the-counter analgesics.  The patient has been evaluated by doctors for "joint problems" in the past but declined their treatment recommendations.  He has smoked a pack of cigarettes daily for 30 years.  Vital signs are normal.  Examination findings of the patient's hands are shown in the image below.

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Which of the following pathogenic mechanisms is most likely responsible for this patient's condition?

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This patient has a chronic, symmetric, deforming arthritis consistent with advanced rheumatoid arthritis (RA).  His examination shows classic features including joint enlargement, ulnar deviation at the metacarpophalangeal joints, and swan neck deformities (hyperextension at the proximal interphalangeal joints with flexion at the distal interphalangeal joints).

The joint destruction in RA is thought to be initiated by CD4+ T helper cells and is characterized by synovial hyperplasia and an inflammatory infiltrates (often containing lymphoid follicles).  The joint space often becomes replaced by a synovial pannus, an invasive mass composed of fibroblast-like synovial cells, granulation tissue, and inflammatory cells.  Release of proteinases (eg, matrix metallopeptidase 13) causes destruction of the articular cartilaginous matrix, facilitating erosion of the surrounding articular cartilage and underlying bone.  Ossification of the pannus can lead to fusion of the bones across the affected joint (bony ankylosis).

(Choices A and E)  Calcific degeneration of the articular cartilage (chondrocalcinosis) is a characteristic feature of calcium pyrophosphate dihydrate deposition disease (pseudogout).  Deposition of uric acid crystals results in gout.  Both gout and pseudogout are inflammatory arthritides that can cause pain and joint deformation but present with acute, episodic arthritis and are more common in the lower extremities.

(Choice B)  Osteoarthritis is characterized by progressive fracturing and erosion of the articular cartilage.  Periarticular findings include osteophyte formation and subchondral sclerosis.  When osteoarthritis affects the hands, it typically presents with bony enlargement at the proximal and distal interphalangeal joints (Bouchard and Heberden nodes, respectively) rather than ulnar deviation at the metacarpophalangeal joints.

(Choice C)  Autoimmune complex deposition (type III hypersensitivity) plays a significant role in the arthritis associated with systemic lupus erythematosus.  Although lupus may cause a chronic destructive arthritis resembling RA in a minority of cases, lupus arthritis is typically migratory, nondeforming, and much more common in younger women than in older men.

Educational objective:
Joint destruction in rheumatoid arthritis is characterized by synovial hyperplasia, an inflammatory infiltrate, and synovial angiogenesis.  The joint space often becomes replaced by pannus, an invasive mass composed of fibroblast-like synovial cells, granulation tissue, and inflammatory cells that can erode into the articular cartilage and underlying bone.