Which triad best describes extremity symptoms in sickle cell disease?

• A. Weakness
• B. Peripheral neuropathy and weakness
• C. Arthralgia only
• D. Weakness, Peripheral neuropathy, Arthralgias

Answer: (D)

In sickle cell disease, extremity symptoms arise from multiple linked effects of the disease on blood flow, nerves, and joints. Chronic anemia from hemolysis leads to fatigue and weakness because tissues aren’t getting enough oxygen. Vaso-occlusive processes repeatedly block small vessels in bones and joints, causing painful arthralgias and conditions like dactylitis in the extremities. Nerve tissue can also suffer from ischemia due to these occlusions, leading to peripheral neuropathy with sensory changes or weakness.

Seeing all three together—weakness from anemia, peripheral neuropathy from nerve ischemia, and arthralgia from joint/bone ischemia—best captures the common pattern of extremity involvement in sickle cell disease. A single symptom on its own doesn’t reflect the full spectrum: weakness alone misses nerve and joint pain; neuropathy with weakness omits the joint pain; arthralgia alone omits systemic fatigue and nerve involvement.