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Inflammation of Unknown Origin (1st Pass)

❓What❓

  • “Inflammation of unknown origin” (IUO) refers to the patient presenting with any combination of symptoms/signs suggestive of inflammation without accompanying localizing symptoms for infection (e.g. cough, abdominal pain), & whose symptoms/signs are persisting longer than a self-limited condition (e.g. viral URI)

  • While the name of this diagnostic conundrum is borrowed from the “FUO” literature, we intentionally broaden the definition to “inflammation” given fevers may not be captured during outpatient presentations to care, & given accompanying inflammatory lab markers can further corroborate the problem

  • The approach to IUO has multiple diagnostic phases, the first of which (”1st pass”) is identical to the classical FUO approach, which emphasizes a search for bloodstream infection, occult pyogenic infections, & clues that suggest a need to move onto the “2nd pass” (e.g. atypical infections, malignancies, autoimmune diseases)

❓Presentation❓

Clinical 🔥

  • Fever (constitutive vs. cyclic)
  • Chills, rigors
  • Malaise, nausea, vomiting

Laboratory 🔬

  • ↑ WBC (acute), ↑ platelet (chronic), ↓ hemoglobin (myelosuppression)
  • ↑ CRP (acute), ↑ ESR (chronic), ↑ procalcitonin (pyogenic)

❓Approach❓

Bloodwork: Signal Searching 👀

  • ESR/CRP: severity of inflammation (e.g. ESR > 100?)
  • CBC: interesting cell differential (e.g. atypical lymphocytosis, eosinophilia)?
  • BMP: renal involvement (e.g. vasculitis)?
  • LFTs: hepatic infiltration (↑ ALP > bilirubin), hepatitis (↑ ALP = ↑ bilirubin)?
  • BCx: blood stream vs. endovascular infection?
  • UA → UCx: urinary tract infection?

⚪ Note: an ESR > 100 is associated with a low false ⊕ rate for serious underlying disease, with pyogenic infection being the leading cause (see separate teaching page)

Cross-sectional Imaging: Occult Abscess 🎭

  • CT chest w/ IV contrast: pneumonia is “CXR ⊖” in ~15-30%
  • CT abdomen & pelvis w/ IV contrast: liver abscess (100% sensitive)

Hepatic abscess due to strep. anginosus, found in patient who presented for fever & malaise (no abdominal pain) several months after an uncomplicated intraabdominal surgery
Hepatic abscess due to strep. anginosus, found in patient who presented for fever & malaise (no abdominal pain) several months after an uncomplicated intraabdominal surgery

⊕/⊖

  • HIDA scan: cholecystitis should be suspected if mild ↑ in AST/ALT/ALP (contiguous inflammation), & in geriatric or neuropathy patients with unexplained neutrophilic leukocytosis despite ⊖ CT imaging (sensitivity ~85%)

image

  • MRI total spine w/wo IV contrast: epidural abscess should be suspected if high-risk host due to active comorbidities (hardware, IV drug use, DM, ESKD, cirrhosis), past comorbidities (recent bacteremia, spinal instrumentation), & patients with ESR > 100, particularly if new, subacute neck/back pain. (Notably, accompanying WBC is often underwhelming.) While CT for the detection of spondylodiscitis carries a sensitivity of ~80%, it is <10% sensitive for epidural abscess, thus MRI is exceedingly preferred (sensitivity ~95%)

A 56-year-old man presented with a 2-week history of thoracic back pain and a 5-day history of progressive weakness and numbness of the legs and feet. MRI (Panel B, axial T2-weighted; Panel C, axial T1-weighted postcontrast with fat saturation at the level of T6–T7; Panel D, sagittal T1-weighted postcontrast with fat saturation) shows enhancement of the T6–T7 vertebral bodies (black arrows) and T6–T7 interspace indicating discitis osteomyelitis. Flagrant enhancing ventral paraspinal abscess (white arrow) displaces the great vessels anteriorly, and right lateral ventrolateral epidural abscess (short white arrows) causes advanced spinal canal stenosis and deformity of the cord. Enhancing ventral and dorsal (short black arrows) epidural phlgemon extends from T5 to T9.
A 56-year-old man presented with a 2-week history of thoracic back pain and a 5-day history of progressive weakness and numbness of the legs and feet. MRI (Panel B, axial T2-weighted; Panel C, axial T1-weighted postcontrast with fat saturation at the level of T6–T7; Panel D, sagittal T1-weighted postcontrast with fat saturation) shows enhancement of the T6–T7 vertebral bodies (black arrows) and T6–T7 interspace indicating discitis osteomyelitis. Flagrant enhancing ventral paraspinal abscess (white arrow) displaces the great vessels anteriorly, and right lateral ventrolateral epidural abscess (short white arrows) causes advanced spinal canal stenosis and deformity of the cord. Enhancing ventral and dorsal (short black arrows) epidural phlgemon extends from T5 to T9.

Cross-sectional Imaging: Gateway ✨

  • To summarize, the first major rationale for cross-sectional imaging is to EXCLUDE an occult pyogenic infection, with the potential addition of the HIDA scan vs. MRI spine in patients with specific risk factors or suggestive clinical signature

  • The second major rationale for cross-sectional imaging is to SCREEN for clues that will be utilized in the NEXT diagnostic phase (”2nd pass”), such as diffuse lymphadenopathy

📚 References 📚