Internal Medicine · Year 3 · from Internal Medicine
Case 1: Fever of Unknown Origin
Patient Presentation
A 54-year-old man presents with a 4-week history of daily fevers ranging from 38.3°C to 39.2°C. He reports night sweats, fatigue, and an unintentional 10-pound weight loss. He has no localizing symptoms such as cough, dysuria, abdominal pain, or rash. He works as an accountant, has no recent travel, and has no sick contacts. Past medical history includes hypertension controlled with lisinopril.
Vital Signs
- Blood Pressure: 128/78 mmHg
- Heart Rate: 92 bpm
- Respiratory Rate: 16/min
- Oxygen Saturation: 98% on room air
- Temperature: 38.9°C
Physical Examination
- General: Appears fatigued but not toxic
- HEENT: No oral lesions, no lymphadenopathy
- Cardiovascular: Regular rhythm, no murmurs
- Pulmonary: Clear to auscultation
- Abdomen: Splenomegaly palpable 3 cm below costal margin
- Skin: No rashes, no petechiae
Initial Workup
- CBC: WBC 11,200/μL, Hgb 10.2 g/dL, Platelets 420,000/μL
- ESR: 85 mm/hr (normal <20)
- CRP: 12.4 mg/dL (normal <0.5)
- LDH: 380 U/L (elevated)
- Blood cultures: Pending
- Urinalysis: Normal
- Chest X-ray: No infiltrates or masses
- CT Abdomen/Pelvis: Splenomegaly, multiple enlarged retroperitoneal lymph nodes
Clinical Image
Figure 1: Axial CT scan of the abdomen demonstrating multiple enlarged retroperitoneal lymph nodes (arrows) in a patient with fever of unknown origin subsequently diagnosed with lymphoma.
Image Source: Educational illustration for teaching purposes.
Questions
- What criteria define classic fever of unknown origin (FUO)?
- A) Temperature >38.3°C for >1 week without diagnosis after initial workup
- B) Temperature >38.3°C for >3 weeks with no diagnosis after 3 days inpatient or 3 outpatient visits
- C) Temperature >39°C for >2 weeks with negative blood cultures
- D) Temperature >38°C for >1 week in a hospitalized patient
- What are the four major categories of causes for classic FUO?
- A) Bacterial, viral, fungal, parasitic
- B) Infectious, neoplastic, autoimmune/inflammatory, miscellaneous
- C) Cardiac, pulmonary, abdominal, neurologic
- D) Acute, subacute, chronic, recurrent
- Given the findings of splenomegaly, lymphadenopathy, elevated LDH, and constitutional symptoms, what diagnosis is most likely?
- A) Systemic lupus erythematosus
- B) Tuberculosis
- C) Lymphoma
- D) Endocarditis
- What is the most appropriate next diagnostic step?
- List three infectious causes of FUO that should be considered in all patients.
Answers
- B) Temperature >38.3°C for >3 weeks with no diagnosis after 3 days inpatient or 3 outpatient visits - Classic FUO requires fever duration >3 weeks and failure to reach diagnosis despite adequate initial investigation.
- B) Infectious, neoplastic, autoimmune/inflammatory, miscellaneous - These four categories account for most cases of FUO. In developed countries, the proportion of neoplastic and autoimmune causes has increased while infections have decreased.
- C) Lymphoma - The constellation of fever, night sweats, weight loss (B symptoms), splenomegaly, lymphadenopathy, elevated LDH, and anemia strongly suggests lymphoma, particularly Hodgkin lymphoma or aggressive non-Hodgkin lymphoma.
- Next diagnostic step: Excisional lymph node biopsy of an accessible retroperitoneal node (CT-guided or surgical) is the most appropriate step. Fine needle aspiration is inadequate for lymphoma diagnosis as architectural assessment is required for classification.
- Infectious causes of FUO to consider:
- Tuberculosis (pulmonary and extrapulmonary)
- Endocarditis (especially culture-negative)
- Intra-abdominal abscess
- Osteomyelitis
- HIV infection
- Cytomegalovirus
- Epstein-Barr virus