Differential Diagnosis for a 14-year-old boy with fatigue, sore throat, fever, posterior cervical lymphadenopathy, and splenomegaly

• Single most likely diagnosis:
  • Infectious Mononucleosis (Mono) caused by Epstein-Barr Virus (EBV). This diagnosis is most likely due to the combination of symptoms such as sore throat, fever, posterior cervical lymphadenopathy, and splenomegaly, which are classic for EBV infection. The age of the patient also fits within the common range for developing mono.
• Other Likely diagnoses:
  • Streptococcal Pharyngitis: Although the presence of splenomegaly is not typical, streptococcal infections can cause significant lymphadenopathy and fever. The sore throat could be a primary symptom.
  • Acute Lymphoblastic Leukemia (ALL) or Lymphoma: These conditions can present with lymphadenopathy, splenomegaly, and systemic symptoms like fatigue and fever. Although less common than infectious causes, they are critical to consider in the differential diagnosis.
• Do Not Miss diagnoses:
  • Hemophagocytic Lymphohistiocytosis (HLH): A rare but life-threatening condition that can be triggered by infections, including EBV. It presents with fever, lymphadenopathy, splenomegaly, and can progress rapidly.
  • Acute Leukemia: Similar to ALL, other forms of leukemia can present with nonspecific symptoms and signs such as fatigue, fever, lymphadenopathy, and splenomegaly.
• Rare diagnoses:
  • Toxoplasmosis: Although more commonly associated with immunocompromised patients, toxoplasmosis can cause lymphadenopathy and occasionally splenomegaly in immunocompetent individuals.
  • Cytomegalovirus (CMV) Infection: Similar to EBV, CMV can cause a mononucleosis-like syndrome with fever, lymphadenopathy, and splenomegaly, but it's less common in this age group without specific risk factors.
  • Brucellosis: A zoonotic infection that can cause fever, lymphadenopathy, and splenomegaly, but it's rare and usually associated with specific exposures (e.g., contact with infected animals).

Given the clinical presentation, avoidance of contact sports is the most appropriate initial recommendation to prevent the risk of splenic rupture, which can be a complication of splenomegaly, particularly if the diagnosis is indeed infectious mononucleosis. Amoxicillin therapy could be considered if streptococcal pharyngitis is confirmed, but it's not appropriate for EBV. Hospitalization for monitoring might be necessary depending on the severity of symptoms and the evolution of the disease. Corticosteroid therapy is not typically the first-line treatment for these conditions but might be considered in specific scenarios, such as severe airway obstruction in infectious mononucleosis or in the treatment of certain hematologic malignancies.