Fever of Unknown Origin

1
Fever of Unknown Origin

• Temperature elevation of 101 F (38.3 C) or
  higher for 3 weeks or longer, the cause of which
  is not diagnosed after 1 week of inpatient
  evaluation.
• Revised to include one week of outpatient
  workupminimum to include HP, repeated PE, CBC,
  chem 10, LFTs, LDH, UA, CXR, ESR, ANA, RF, ACE
  level, Blood Cx times three off Abx, assay for
  CMV viremia, heterophile Ab, TB skin test, CT of
  belly, HIV assay.

2
History Taking

• Medication history. Common offenders sulfa,
  PCN, nitrofurantoin, antimalarials, H2 blockers,
  phenytoin, iodides, hydralazine, methyldopa,
  quinidine, procainamide, PTU
• Tick exposure (rickettsial, lyme)
• Animal contact (Psittacosisbirds
  Leptospirosisrat urine Brucellosisgoats,
  sheep, cattle, hogs, dogs Toxoplasmosis or Cat
  Scratch Fevercats Q fevercattle, sheep,
  goats Rat bite feverrodents)

3
History Taking

• Travel Historyweird infections
• Family Historyautoimmune, malignancy
• Any immunosuppressive conditionsmedications
  (prednisone), diabetes, alcoholism, malnutrition
• Specific symptomsfatigue, weight loss, myalgias,
  cough, abdominal pain, headache, confusion, rash
• Of note, pattern of the fever not specific enough
  to guide the workup

4
Physical Exam What to look for

• Vitals signsincluding relative bradycardia
• HEENTdry eyes, conjunctivitis, hemorrhages,
  uveitis
• Cardiacmurmur
• Hepatosplenomegaly
• Rash
• Lymphadenopathy
• Tendernessmuscular, joint, spinal

5
Differential Diagnosis

• Think of this as disease entities that can hide
  from our usual workup, or be difficult to
  diagnose.
• For example occult intrabdominal abcess in an
  elderly patientmay not manifest with typical
  abdominal pain, tenderness.
• TB difficult to diagnose because of the prolonged
  culture time for mycobacteria.
• Also, better culture techniques and better
  serologic testing have made previous FUO big
  hitters more rarei.e. culture negative
  endocarditis, lupus.

6
Differential Diagnosis The Big 3

• Infectious TB, endocarditis, CMV, occult
  abscess, osteomyelitis, sinusitis, prostatitis,
  gallbladder
• Malignancy lymphoma, renal cell ca, atrial
  myxoma, hepatoma or mets to liver
• Collagen Vascular the usual, and in particular
  temporal arteritis, adult Stills disease also
  (under vascular) embolic disease such as PE,
  cholesterol emboli

7
Differential Diagnosis The Worrisome Ones

• In large series, these are the things that
  patients are more likely to DIE OF before a
  definitive diagnosis is established.
• Infectious disseminated TB, disseminated fungal
  infection
• Malignancy lymphoma
• Collagen Vascular PE or other serious embolic
  event

8
Workup

• Initial evaluation thorough HP, CBC, ESR,
  LFTs, UA, CXR, Abd CT, cultures
• Follow up and pursue abnormalities found on the
  above evaluation. Many times tissue is the
  issue!
• --image the affected area
• --biopsy any suspicious lymph nodes, skin
  lesions, organ involvement
• --bronchoscopy in pulmonary disease
• --if miliary TB or cancer suspected, perform
  bone marrow biopsy

9
Treatment

• Obviously, has to be geared towards your
  diagnosis.
• Empiric antibiotics may only confuse the picture.
  In general, not indicated unless the patient is
  immune suppressed or septic.
• What if a patient remains undiagnosed despite
  extensive evaluation?
• There is good literature support that these
  patients generally do well.
• They can simply be followed over time, and any
  new signs/symptoms pursued.
• Prolonged viral syndrome nos is thought to be
  the cause in many cases.