Fever of unknown origin: Difference between revisions

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==Differential Diagnosis==
==Differential Diagnosis==
*Infectious disease (22%)
====Infections (~30%)====
**[[EBV]]
*'''Abscess'''
**[[UTI]]
**Intra-abdominal [[abscess]] (hepatic, subphrenic, pelvic, perinephric)
**Enterovirus
**[[Epidural abscess]]
**[[Lyme]]
**Dental abscess
**[[Cat-scratch disease]]
**[[Prostatitis]]
*'''Endovascular'''
**[[Endocarditis]]
**Infected vascular graft/device
**Mycotic aneurysm
*'''Mycobacterial'''
**[[Tuberculosis]] (pulmonary and extrapulmonary)
**Nontuberculous mycobacteria (MAC)
*'''Viral'''
**[[EBV]] (mononucleosis)
**[[CMV]]
**[[HIV]] (acute seroconversion)
**[[Hepatitis B]], [[hepatitis C]]
**[[COVID-19]]
*'''Fungal'''
**[[Histoplasmosis]]
**[[Coccidioidomycosis]]
**[[Blastomycosis]]
**[[Cryptococcosis]]
**[[Aspergillosis]] (immunocompromised)
*'''Parasitic'''
**[[Malaria]]
**[[Toxoplasmosis]]
**Visceral leishmaniasis
**Amebiasis (liver abscess)
*'''Bacterial'''
**[[Osteomyelitis]]
**[[Osteomyelitis]]
**[[Psittacosis]]
**[[Pyelonephritis]]/renal abscess
**[[Rheumatic fever]]
**[[Cholangitis]]
**[[Crohn's]]
**[[Sinusitis]] (chronic)
**Bacterial [[meningitis]]
**[[Brucellosis]]
*Autoimmune (6%)
**[[Q fever]] ([[Coxiella burnetii]])
**JRA
**[[Lyme disease]]
**[[SLE]]
**[[Cat scratch disease]] (''Bartonella'')
**PAN
**[[Syphilis]]
*Malignancy (2%)
**[[Whipple's disease]]
**Leukemia
**[[Rat-bite fever]]
**Lymphoma
 
*Drug-induced fever (2%)
====Malignancy (~20%)====
*Factitious (2%)
*'''Hematologic''' (most common malignant cause of FUO)
*No Etiology  (67%)
**[[Lymphoma]] (Hodgkin and non-Hodgkin)
**[[Leukemia]] (especially acute leukemia)
**Multiple myeloma
**Myelodysplastic syndrome
**Castleman disease
*'''Solid Tumors'''
**Renal cell carcinoma
**Hepatocellular carcinoma
**Colon cancer
**Pancreatic cancer
**Atrial myxoma
**Pheochromocytoma
 
====Autoimmune/Inflammatory (~20%)====
*'''Connective Tissue Disease'''
**[[Adult-onset Still's disease]] (AOSD)
**[[Systemic JIA]] (sJIA) — pediatric equivalent
**[[Systemic lupus erythematosus]] (SLE)
**[[Rheumatoid arthritis]]
**[[Polymyositis]]/dermatomyositis
**Mixed connective tissue disease
*'''Vasculitis'''
**Giant cell (temporal) arteritis / polymyalgia rheumatica (especially adults >50)
**[[Polyarteritis nodosa]]
**Granulomatosis with polyangiitis (Wegener's)
**Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
**Takayasu arteritis
**[[Kawasaki disease]] (pediatric)
*'''Granulomatous'''
**[[Sarcoidosis]]
**Crohn's disease / [[inflammatory bowel disease]]
*'''Autoinflammatory/Periodic Fever Syndromes'''
**[[Familial Mediterranean fever]]
**TNF receptor-associated periodic syndrome (TRAPS)
**Hyper-IgD syndrome (HIDS)
**PFAPA syndrome (pediatric)
**Schnitzler syndrome
*'''Other'''
**[[Macrophage activation syndrome]] (MAS) / [[hemophagocytic lymphohistiocytosis]] (HLH)
**Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)
 
====Drug Fever====
*[[Antibiotics]] (beta-lactams, sulfonamides, nitrofurantoin)
*[[Anticonvulsants]] (phenytoin, carbamazepine)
*[[Allopurinol]]
*[[Heparin]]
*Procainamide
*[[DRESS syndrome]]
*[[Serotonin syndrome]]
*[[Neuroleptic malignant syndrome]]
*Chemotherapy/biologic agents
 
====Endocrine/Metabolic====
*[[Thyrotoxicosis]] / [[thyroid storm]]
*[[Adrenal insufficiency]]
*[[Pheochromocytoma]]
*Hypertriglyceridemia (rarely)
 
====Thromboembolic/Vascular====
*[[Pulmonary embolism]]
*[[Deep vein thrombosis]]
*Hematoma (retroperitoneal, intramuscular)
*Aortic dissection (rarely)
 
====Factitious/Habitual====
*Factitious fever (self-induced)
*Munchausen syndrome / Munchausen by proxy (pediatric)
 
====Miscellaneous====
*Post-surgical/post-procedural inflammation
*[[Gout]]/pseudogout (crystal arthropathy)
*Cirrhosis / [[alcoholic hepatitis]]
*Hemolytic anemia
*Transfusion reaction
*[[Tissue necrosis]] (rhabdomyolysis, large hematoma, pancreatitis)
*Hypothalamic dysfunction (central fever)
*Periodic fever of unknown cause (~10-15% of FUO never diagnosed)


==Evaluation==
==Evaluation==

Revision as of 19:28, 9 March 2026

This page is for adult patients. For pediatric patients, see: fever of unknown origin (peds)

Background

Clinical Features

Differential Diagnosis

Infections (~30%)

Malignancy (~20%)

  • Hematologic (most common malignant cause of FUO)
    • Lymphoma (Hodgkin and non-Hodgkin)
    • Leukemia (especially acute leukemia)
    • Multiple myeloma
    • Myelodysplastic syndrome
    • Castleman disease
  • Solid Tumors
    • Renal cell carcinoma
    • Hepatocellular carcinoma
    • Colon cancer
    • Pancreatic cancer
    • Atrial myxoma
    • Pheochromocytoma

Autoimmune/Inflammatory (~20%)

Drug Fever

Endocrine/Metabolic

Thromboembolic/Vascular

Factitious/Habitual

  • Factitious fever (self-induced)
  • Munchausen syndrome / Munchausen by proxy (pediatric)

Miscellaneous

  • Post-surgical/post-procedural inflammation
  • Gout/pseudogout (crystal arthropathy)
  • Cirrhosis / alcoholic hepatitis
  • Hemolytic anemia
  • Transfusion reaction
  • Tissue necrosis (rhabdomyolysis, large hematoma, pancreatitis)
  • Hypothalamic dysfunction (central fever)
  • Periodic fever of unknown cause (~10-15% of FUO never diagnosed)

Evaluation

Workup

Phase 1

Phase 2

Phase 3

  • Abd ultrasound
  • Abd CT
  • Gallium/Indium scanning
  • UGI series with sbft
  • Bone marrow
  • Technetium bone scan

Management

Disposition

See Also

References

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