Differential Diagnosis for a 45-year-old Male with Intermittent Fever and Hepatosplenomegaly
Single Most Likely Diagnosis
- Infectious Mononucleosis (IMN) or Chronic Active Epstein-Barr Virus (EBV) Infection: Although the patient's age is somewhat higher than typical for IMN, the presentation of intermittent fever, mild elevation of liver enzymes, and hepatosplenomegaly, along with a prolonged course, could suggest a chronic or reactivated EBV infection. The normal CBC and lack of significant lymphocytosis do not rule out this diagnosis, especially in adults who may have atypical presentations.
Other Likely Diagnoses
- Lymphoma (Hodgkin or Non-Hodgkin): The presence of hepatosplenomegaly, intermittent fever, and elevated CRP suggests a possible lymphoproliferative disorder. Lymphoma can present with a wide range of symptoms, including fever of unknown origin (FUO) and hepatosplenomegaly.
- Tuberculosis (TB): Although blood cultures are negative, TB can cause a chronic infection with intermittent fever, hepatosplenomegaly, and elevated inflammatory markers. The absence of a clear pulmonary focus on CT does not rule out extrapulmonary TB.
- Endocarditis (Infective): Despite a normal ECHO, the possibility of infective endocarditis, particularly with a more unusual or resistant organism, should be considered. The negative blood cultures could be due to prior antibiotic use or a fastidious organism.
Do Not Miss Diagnoses
- Brucellosis: This zoonotic infection can cause fever, hepatosplenomegaly, and elevated liver enzymes. Given the patient's residence in western North Carolina, exposure to infected animals is possible. Brucellosis is a diagnosis that can be easily missed but is critical due to its potential for serious complications if untreated.
- Histoplasmosis or Other Fungal Infections: In a patient from the southeastern United States, histoplasmosis is a consideration, especially with symptoms of fever and hepatosplenomegaly. Other fungal infections could also be considered, given the geographic location and clinical presentation.
- Malignant Histiocytosis or Hemophagocytic Lymphohistiocytosis (HLH): These are rare but life-threatening conditions that can present with fever, hepatosplenomegaly, and elevated inflammatory markers. A high index of suspicion is required, as these conditions can mimic other diseases and have a high mortality if not promptly treated.
Rare Diagnoses
- Whipple's Disease: A rare, systemic bacterial infection that can cause fever, weight loss, hepatosplenomegaly, and elevated inflammatory markers. Diagnosis is often delayed due to its rarity and nonspecific presentation.
- Castleman Disease: A rare disorder that can cause fever, hepatosplenomegaly, and elevated inflammatory markers. It can be unicentric or multicentric and may be associated with lymphoma or human herpesvirus 8 (HHV-8) infection.
- Sarcoidosis: Although more commonly associated with pulmonary symptoms, sarcoidosis can cause hepatosplenomegaly and fever. The diagnosis would typically be supported by biopsy findings of non-caseating granulomas.