A 10-month-old male infant presents with acute onset of painful swelling and erythema of both hands and feet over 24 hours. The child was well until 6 months of age. On examination, there is symmetric edema and tenderness of the metacarpals and metatarsals bilaterally. The structure marked **C** in the diagram indicates the typical age of presentation for this condition. Hemoglobin electrophoresis confirms HbSS sickle cell disease. Apart from acute management with hydration and analgesia, which of the following is the most important disease-modifying intervention to prevent recurrent vaso-occlusive crises in this infant?

Explanation

## Why Initiation of hydroxyurea therapy is right Hand-foot syndrome (dactylitis) is the classic first presentation of sickle cell disease in infants aged 6–24 months, occurring as fetal hemoglobin (HbF) is replaced by HbS. The marked structure **C** identifies this critical age window. Hydroxyurea is a disease-modifying agent that increases HbF production, reduces sickling, and decreases vaso-occlusive crises, acute chest syndrome, and transfusion requirements. The BABY HUG trial demonstrated that hydroxyurea is safe and effective in infants ≥9 months with HbSS disease, making it the standard of care for primary prevention in this age group. This patient, now 10 months old, is at the ideal age to initiate hydroxyurea to prevent recurrent crises. ## Why each distractor is wrong - **Chronic monthly blood transfusions**: While transfusions are indicated for specific complications (e.g., elevated transcranial Doppler velocity for stroke prevention via the STOP trial, or recurrent acute chest syndrome), they are not first-line disease-modifying therapy in newly diagnosed infants. Transfusions carry risks of iron overload, alloimmunization, and infection. - **Splenectomy**: The spleen is already functionally asplenic in sickle cell disease due to repeated infarctions; surgical splenectomy is not indicated and does not prevent vaso-occlusive crises. Penicillin prophylaxis and vaccination are the preventive measures for pneumococcal sepsis. - **Bone marrow transplantation**: Although HLA-matched sibling transplantation is curative (~85–95% success in children), it is reserved for severe disease or those with complications, not for initial management of hand-foot syndrome. It carries significant morbidity and mortality and is not offered to all newly diagnosed patients. **High-Yield:** Hand-foot syndrome at 6–24 months is the first presentation of sickle cell disease; hydroxyurea initiated at ≥9 months is disease-modifying and standard of care per BABY HUG trial. [cite: Nelson Textbook of Pediatrics 21e Ch 489; Robbins and Cotran Pathologic Basis of Disease 10e Ch 14]