Differential Diagnosis of Generalized Lymphadenopathy

The differential diagnosis for generalized lymphadenopathy is broad and can be categorized based on the likelihood and potential impact of missing a diagnosis. Here's a structured approach:

• Single Most Likely Diagnosis

  • Infectious Mononucleosis: This is often the first consideration due to its relatively high prevalence, especially in young adults. The disease, caused by Epstein-Barr virus (EBV), presents with fever, sore throat, fatigue, and generalized lymphadenopathy.

• Other Likely Diagnoses

  • Tuberculosis (TB): A significant cause of lymphadenopathy worldwide, especially in endemic areas. It can present with systemic symptoms like fever, night sweats, and weight loss, alongside lymph node enlargement.
  • HIV Infection: Early stages of HIV can manifest with generalized lymphadenopathy, among other symptoms like fever, rash, and sore throat.
  • Lymphoma: Both Hodgkin and non-Hodgkin lymphoma can present with generalized lymphadenopathy, often accompanied by systemic symptoms such as fever, night sweats, and weight loss.
  • Autoimmune Disorders (e.g., Rheumatoid Arthritis, Systemic Lupus Erythematosus): These conditions can cause lymphadenopathy as part of their systemic manifestations.

• Do Not Miss Diagnoses

  • Malignant Lymphoma (including Burkitt Lymphoma): Although included in "Other Likely Diagnoses," it's crucial to emphasize that missing a diagnosis of lymphoma can have severe consequences due to the need for prompt treatment.
  • Acute Leukemia: Presentation can include lymphadenopathy, and missing this diagnosis can lead to significant morbidity and mortality if not treated promptly.
  • Sarcoidosis: A systemic granulomatous disease that can cause lymphadenopathy, among other symptoms. It's less common but important not to miss due to its potential for serious organ involvement.

• Rare Diagnoses

  • Castleman Disease: A rare disorder that can cause lymphadenopathy, often with systemic symptoms. It exists in unicentric and multicentric forms, with the latter being more aggressive.
  • Kikuchi-Fujimoto Disease: A rare, self-limiting condition that causes lymphadenopathy, typically in the neck, and is more common in young women.
  • Kimura Disease: A chronic inflammatory disorder that can cause lymphadenopathy and eosinophilia, more commonly seen in Asian males.
  • Whipple's Disease: A rare, systemic bacterial infection that can cause lymphadenopathy, among other symptoms like diarrhea, weight loss, and arthralgias.

Each of these diagnoses has a unique set of clinical features, laboratory findings, and imaging characteristics that can help guide the diagnostic process. A thorough history, physical examination, and appropriate diagnostic tests are essential for narrowing down the differential diagnosis and establishing a definitive diagnosis.