Fever of Unknown Origin Causes

Aka: Fever of Unknown Origin Causes, Persistent Fever Causes

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II. Background

  1. Most cases of Fever of Unknown Origin are by a limited list of common causes presenting uncommonly (see below)

III. Causes: Common

  1. Infectious common causes (20-40% of cases)
    1. Bacterial common causes
      1. Abdominal or pelvic abscess
      2. Cat Scratch Disease
      3. Dental abscess
      4. Endocarditis
      5. Osteomyelitis
      6. Sinusitis
      7. Tick-Borne Disease (e.g. Lyme Disease, Anaplasmosis, Babesiosis, Tickborne Relapsing Fever)
      8. Tuberculosis (esp. Extrapulmonary Tuberculosis)
      9. Urinary Tract Infection
    2. Viral common causes
      1. Epstein Barr Virus (EBV)
        1. Accounts for 50% children with Fever of Unknown Origin (most common <6 years old)
        2. Consider even in the absence of Pharyngitis and Lymphadenopathy
      2. Cytomegalovirus
      3. Acute HIV Infection
  2. Cancer common causes (20-30% of cases)
    1. Leukemia
    2. Lymphoma
    3. Colorectal Cancer
  3. Inflammatory common causes (10-30% of cases)
    1. Connective Tissue Disease
      1. Still's Disease
      2. Rheumatoid Arthritis
      3. Systemic Lupus Erythematosis
    2. Granulomatous disease
      1. Crohn's Disease
      2. Sarcoidosis
    3. Vasculitic disease
      1. Polymyalgia Rheumatica or Giant Cell Arteritis
  4. Miscellaneous (10-20% of cases)
    1. Drug-Induced Fever
    2. Factitious fever
    3. Venous Thromboembolism
    4. Thyroiditis

IV. Causes: Viral Infections

  1. Cytomegalovirus
  2. Epstein-Barr Virus (Mononucleosis)
  3. Acute HIV Infection

V. Causes: Bacterial Infections

  1. Systemic infection
    1. Septicemia
    2. Streptococcosis
  2. Vector Borne Disease, Foodborne Disease, or other animal vectors
    1. Lyme Disease
    2. Malaria
    3. Anaplasmosis
    4. Babesiosis,
    5. Typhoid Fever or Enteric Fever
    6. Psittacosis
    7. Brucellosis
    8. Cat Scratch Disease
  3. Head and neck infection
    1. Acute Sinusitis
    2. Dental Abscess
    3. Tonsillitis or Peritonsillar Abscess
    4. Herpes Simplex Virus (including HSV Encephalitis)
  4. Chest infection
    1. Pneumonia
    2. Subacute Bacterial Endocarditis (SBE)
    3. Tuberculosis
  5. Gastrointestinal infection
    1. Liver or biliary Infection
    2. Abdominal or Pelvic Abscess
  6. Genitourinary infection
    1. Pyelonephritis or Urinary Tract Infection
    2. Gonorrhea (may present as Gonococcal Arthritis)
    3. Prostatitis
  7. Musculoskeletal infection
    1. Osteomyelitis
  8. Neurologic infection
    1. Meningitis
    2. Encephalitis

VI. Causes: Neoplastic Disease

  1. Leukemia
  2. Lymphoma
  3. Sarcoma
  4. Carcinomatosis
  5. Renal Cell Carcinoma
  6. Colon Cancer
  7. Pancreatic carcinoma
  8. Hepatoma
  9. Metastatic cancer

VII. Causes: Autoimmune Disease

  1. See Fever in Rheumatic Disease
  2. Juvenile Rheumatoid Arthritis (evanescent rash)
  3. Henoch-Schonlein Purpura
  4. Systemic Lupus Erythematosus
  5. Rheumatic Fever (Migratory polyarthritis)
  6. Polymyalgia Rheumatica
  7. Temporal Arteritis
  8. Inflammatory Bowel Disease
  9. Reiter's Syndrome

VIII. Causes: Heritable Disease

  1. Fabry's Disease
  2. Familial Mediterranean fever
  3. Lamellar Ichthyosis
  4. Nephrogenic Diabetes Insipidus
  5. Anhydrotic ectodermal dysplasia
  6. Familial Dysautonomia

IX. Causes: Granulomatous Disease

  1. Sarcoidosis
  2. Granulomatous Hepatitis
  3. Inflammatory Bowel Disease

X. Causes: Medication (1-3% of cases)

  1. See Drug-Induced Fever

XI. Causes: Miscellaneous

  1. Factitious Fever (Munchausen by proxy)
  2. Thyroiditis
  3. Neurogenic Fever
  4. Milk Allergy
  5. Behcet's Syndrome
  6. Anicteric Hepatitis
  7. Pulmonary Embolism
  8. Deep Vein Thrombosis

XII. References

  1. David (2022) Am Fam Physician 105(2): 137-43 [PubMed]
  2. Hersch (2014) Am Fam Physician 90(2): 91-6 [PubMed]
  3. Zenone (2006) Scand J Infect Dis 38(8): 632-8 [PubMed]

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