Determining the Cause

Chief Complaint: Fever

a. History: Chronic

Differential Diagnosis

  1. Infections: – TB (especially extrapulmonary), abscesses, endocarditis, typhoid, brucellosis, viral infections, HIV

    2. Malignancies - Lymphoma, leukemia, renal cell carcinoma, hepatocellular carcinoma

    3. Autoimmune / Inflammatory – Temporal arteritis, SLE, rheumatoid arthritis, adult-onset Still’s disease, vasculitides

    4. Miscellaneous – Drug fever, thyroiditis, DVT/PE, sarcoidosis, familial Mediterranean fever

  3.  

Next Pivotal Assessment Finding

Further History

Travel

Animal Exposure

Lives in a Crowded Place

Health Worker

Poor Dentition

Implanted Device/Prosthetics

Ingestion of Contaminated Food

  • Drug history (drug fever)

  • TB exposure

  • Implants, prosthetics

  • Occupational (farm, healthcare)

  • Autoimmune symptoms: jaw claudication, morning stiffness, rash, joint pain

  • Weight loss, sweats (malignancy/infection)

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  1.  

⭐ STEPWISE APPROACH

1. Detailed History

This is the most important step.

  •  

2. Complete Physical Exam

Look for subtle clues:

  • Lymphadenopathy

  • Heart murmurs (endocarditis)

  • Skin lesions (Janeway lesions, rash of Still’s disease)

  • Abdominal tenderness or organomegaly

  • Temporal artery tenderness

  • Joint swelling

⭐ 3. First-Line Tests

These rule out many common causes.

Laboratory

  • CBC with differential

  • ESR & CRP

  • CMP (liver/kidney)

  • Blood cultures × 3 (over 24 hours)

  • UA and urine culture

  • HIV test

  • TB testing: PPD or IGRA

  • LDH, ferritin (very high >3000 → Still’s disease or lymphoma)

  • Thyroid function (thyroiditis)

  • ANA & RF (autoimmune)

  • CK (myositis)

  • Peripheral smear

Imaging

  • Chest X-ray

  • Abdominal ultrasound

⭐ 4. Second-Line Investigations (based on findings)

If initial tests are inconclusive:

Infection-focused

  • CT chest/abdomen/pelvis → look for abscesses, TB, malignancy

  • Echocardiogram → evaluate endocarditis

  • Repeat blood cultures if suspicion high

  • Hepatitis serologies

  • CMV/EBV PCR

  • Malaria smear (if travel)

Autoimmune / Inflammatory

  • ANCA panel

  • Complement levels

  • SPEP (multiple myeloma)

  • Temporal artery biopsy (if age > 50 with headache or jaw pain)

Malignancy

  • CT scan or PET-CT

  • Bone marrow biopsy (cytopenias, high LDH)

  • Lymph node biopsy if present

⭐ 5. Third-Line or Targeted Workup

If no diagnosis yet:

  • PET-CT (detects inflammation/malignancy)

  • MRI of spine or abdomen if symptoms correlate

  • Liver biopsy if hepatomegaly or abnormal LFTs

  • Bone marrow biopsy

  • Surgical exploration for occult abscess (rare)

⭐ 6. VERY IMPORTANT: Avoid empiric treatments

Do NOT start antibiotics, steroids, or antitubercular therapy unless you have a strong suspicion. These can:

  • Mask symptoms

  • Delay diagnosis

  • Cause complications

Exceptions (start empiric therapy immediately):

  • Neutropenic fever

  • Hemodynamic instability

  • Suspected giant cell arteritis with visual symptoms

⭐ Red Flags Requiring Immediate Action

If any of these occur, expedite investigations and consider hospitalization:

  • Hemodynamic instability

  • Severe weight loss

  • Immunocompromised state

  • Organ dysfunction

  • New neurological symptoms

  • Severe abdominal pain

  • Rash with desquamation

⭐ Summary of Management Approach

  1. Confirm true fever (documented).

  2. Thorough history + exam.

  3. Basic labs and imaging.

  4. Targeted second-line tests.

  5. PET-CT or biopsies if needed.

  6. Avoid empiric therapy unless emergent.

  7. Reassess regularly—the diagnosis eventually appears in most cases.

If you want, I can create a diagnostic algorithm flowchart, or tailor this to pediatric, elderly, or immunocompromised patients.

 

 

Determining the Cause