What is Her Greatest Risk?

A 43-year-old woman comes to the physician complaining of bilateral joint pain and swelling in her hands for the past few months. She reports easy fatigability and loss of energy that has worsened insidiously. It is especially difficult for her to perform daily activities in the morning due to prolonged stiffness. The patient also describes frequent knee pain accompanied by a low-grade fever. She takes over-the-counter ibuprofen to relieve her symptoms. Her hematocrit is 33% and creatinine is normal. This patient is at greatest risk for which of the following?

• A. Avascular bone necrosis

• B. Osteitis deformans

• C. Osteitis fibrosa cystica

• D. Osteoporosis

• E. Osteosarcoma

Correct Answer D.

Diagnosis: Rheumatoid Arthritis (RA)

This patient presents with bilateral joint pain, morning stiffness, low-grade fever, and anemia, consistent with RA.

Genetic/Environmental Predisposition (e.g., HLA-DR4, smoking, infection)
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Autoimmune Trigger → Activation of CD4+ T-cells
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Release of Pro-inflammatory Cytokines (TNF-α, IL-1, IL-6)
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Activation of Synovial Cells (Macrophages, Fibroblasts, B-cells)
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Formation of Autoantibodies (Rheumatoid Factor, Anti-CCP)
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Immune Complex Formation → Synovial Inflammation (Synovitis)
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Pannus Formation

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Hyperplasia of the synovial lining → Invasion of cartilage and bone
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Joint Damage & Erosion → Joint Pain, Swelling, and Deformities

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Inflammation damages the joint, causing bilateral pain and stiffness
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Cytokine Release (TNF-α, IL-1) → Morning Stiffness & Fatigue

Morning stiffness due to cytokine activity during sleep
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Systemic Inflammation → Anemia of Chronic Disease

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Hepcidin increases, reducing iron availability → Hematocrit 33%
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Low-grade Fever

Cytokines (IL-1, IL-6) cause systemic symptoms like fever
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Bone Loss (Osteoclast Activation) → Osteoporosis Risk

Chronic inflammation and future glucocorticoid therapy promote bone resorption
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Reduced Mobility (due to pain) → Further Bone Loss

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Reduced physical activity accelerates bone density loss

Source Image: NEJM

Why Other Options Are Incorrect:

1. Avascular Necrosis (AVN) [Choice A]

   • Cause: Corticosteroid use, heavy alcohol use, SLE, or sickle cell disease

   • Reason for Incorrectness: Although corticosteroids are used in RA, the likelihood of osteoporosis is far greater than AVN in this patient
     

2. Paget’s Disease of Bone (Osteitis Deformans) [Choice B]

   • Cause: Increased bone turnover due to osteoclast overactivity, leading to abnormal woven bone

   • Reason for Incorrectness: Not associated with RA, and this patient's age (43) and symptoms don’t match Paget’s disease
     

3. Osteitis Fibrosa Cystica (Von Recklinghausen disease of bone) [Choice C]

   • Cause: Severe hyperparathyroidism (common in parathyroid carcinoma)

   • Reason for Incorrectness: Very rare, and primarily occurs in patients with hyperparathyroidism; not commonly seen in RA
     

4. Osteosarcoma [Choice E]

   • Cause: Malignant bone tumor; risk factors include Paget’s disease, radiation, chemotherapy

   • Reason for Incorrectness: The patient does not show signs of a malignant tumor or associated risk factors; osteosarcoma usually presents with localized bone pain/swelling

     
     

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