Differential Diagnosis

The patient presents with a complex set of symptoms including swollen lymph nodes, fatigue, appetite loss, nausea, lightheadedness, and fever. Given the duration and progression of symptoms, along with the results of initial tests, we can categorize the differential diagnosis as follows:

• Single Most Likely Diagnosis
  • Chronic Infectious Mononucleosis or Persistent EBV Infection: Despite the initial negative EBV test, the positive mono titer test (1:2) and the clinical presentation could suggest a chronic or reactivated EBV infection. The symptoms of prolonged fatigue, fever, and lymphadenopathy are consistent with this diagnosis. However, the low titer and previous negative EBV test might also suggest a false positive or past infection. (40%)
• Other Likely Diagnoses
  • Lymphoma: Although the ultrasound of one lymph node was unremarkable and LDH, CRP, and ESR were normal, the presence of slowly growing lymph nodes over three years, recent worsening of symptoms, and the appearance of new lymph nodes, including one in the left supraclavicular area, raise concern for lymphoma. A false positive mono test could occur. (30%)
  • Tuberculosis (TB): The chronic nature of symptoms such as fatigue, fever, and lymphadenopathy, along with the lack of response to antibiotics, could suggest TB, especially if the patient has been exposed or is from an endemic area. (15%)
  • Autoimmune Disorders (e.g., Rheumatoid Arthritis, Lupus): These conditions can present with prolonged fatigue, fever, and lymphadenopathy. However, specific autoantibodies and more characteristic symptoms (e.g., joint pain, skin rashes) are usually present. (10%)
• Do Not Miss Diagnoses
  • HIV Infection: Given the prolonged period of symptoms such as fatigue, fever, and lymphadenopathy, HIV should be considered, especially if there are risk factors for HIV exposure. (3%)
  • Other Chronic Infections (e.g., Toxoplasmosis, CMV): These infections can cause similar symptoms, especially in immunocompromised patients. (2%)
• Rare Diagnoses
  • Castleman Disease: A rare disorder that involves an overgrowth of cells in the body's lymph nodes. It can cause fever, fatigue, and lymphadenopathy. (1%)
  • Kikuchi-Fujimoto Disease: A rare, self-limiting condition that can cause lymphadenopathy, fever, and fatigue, more commonly seen in young women. (<1%)
  • Sarcoidosis: Although more commonly associated with lung symptoms, sarcoidosis can cause lymphadenopathy and systemic symptoms like fever and fatigue. (<1%)

Justification

The percentages assigned to each diagnosis are approximate and based on the clinical presentation, test results, and the need to consider both common and potentially life-threatening conditions. The single most likely diagnosis and other likely diagnoses are chosen based on the best fit for the patient's symptoms and test results. The "Do Not Miss" category includes diagnoses that are less likely but critical to identify due to their potential impact on the patient's health. Rare diagnoses are considered but are less likely given the presentation.