What are the causes of acute, subacute, and chronic fever?

Causes of Acute, Subacute, and Chronic Fever

Acute Fever (<3 weeks duration)

Acute fever is predominantly caused by respiratory infections, most commonly viral, followed by exacerbations of underlying diseases and bacterial pneumonia. 1

Primary Causes:

• Viral respiratory tract infections (most common cause, including influenza A) 1
• Bacterial pneumonia 1
• Exacerbations of underlying diseases:
  • Asthma exacerbations 1
  • COPD exacerbations 1
  • Acute bronchitis 1
• Common cold (with productive cough and postnasal drip) 1

Less Common but Important Causes:

• Serious bacterial infections (occur in 3-20% of cases depending on age):
  • Bacteremia 2
  • Meningitis 2
  • Urinary tract infection 2
• Acute infectious causes requiring early antibiotic therapy:
  • Bordetella pertussis 1
  • Chlamydia (TWAR) 1

Non-Infectious Causes:

• Acute irritant or allergic exposures 1

Clinical Pitfall: In critically ill patients, fever may be attributed to non-infectious causes including shock states (cardiogenic, hemorrhagic) that can elevate temperature independent of infection. 3 Drug-induced fever should also be considered, though it typically takes longer to develop. 3

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Subacute Fever (3-8 weeks duration)

Subacute fever is most commonly postinfectious in nature, with postinfectious cough syndrome and exacerbations of underlying respiratory diseases being the predominant causes. 1

Primary Causes:

• Postinfectious cough/fever (most common) 1
• Exacerbations of underlying diseases:
  • Asthma 1
  • COPD 1
  • Upper airway cough syndrome (UACS) 1

Mechanism and Pathophysiology:

• Persistent postnasal drip 1
• Upper airway irritation 1
• Mucous accumulation due to hypersecretion or decreased clearance 1
• Bronchial hyperresponsiveness (transient or asthma-related) 1

Important Considerations:

• Ongoing allergen or irritant exposure 1
• Lingering effects of infections (such as B. pertussis) 1

Management Approach: If subacute fever does not appear postinfectious in nature, it should be evaluated and managed as chronic fever. 1

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Chronic Fever (>8 weeks duration)

Chronic fever has a broad differential diagnosis and is frequently caused by multiple simultaneous conditions, with infectious diseases, rheumatic diseases, and malignancies being the major categories. 1, 4

Infectious Causes (Most Common Category):

Bacterial Infections:

• Focal bacterial infections (most frequent):
  • Urinary tract infections 5
  • Biliary duct infections 5
  • Colonic infections 5
  • Infections of foreign material 5
• Infective endocarditis 5, 4
  • Q fever endocarditis (60-78% of chronic Q fever cases, invariably fatal if untreated) 1
• Tuberculosis 5
• Chronic meningococcemia 5

Parasitic Infections (especially in travelers/migrants):

• Intestinal helminths 1
• Schistosomiasis (Katayama syndrome with dry cough, urticarial rash, fever) 1
• Strongyloidiasis 1
• Filariasis 1

Other Infectious Causes:

• Cytomegalovirus infection 4
• Malaria 5
• Yersinia enterocolitica 5
• Borreliosis 5
• Ratbite fever 5
• Chronic Epstein-Barr virus infection 5

Rheumatic/Autoimmune Diseases (Increasing in Frequency):

• Still's disease 4
• Rheumatic polymyalgia with or without temporal arteritis 4
• Subacute thyroiditis 4

Important Note: Rheumatic diseases are most frequently found in women and the elderly, and their incidence as a cause of chronic fever is rising. 4

Malignant Causes:

• Various oncological and hematological malignancies 6, 4

Chronic Q Fever (Specific Entity):

• Endocarditis (60-78% of chronic Q fever cases) 1
• Vascular infections (aortic aneurysms, vascular grafts - second most common form) 1
• Chronic hepatitis 1
• Osteomyelitis/osteoarthritis 1
• Chronic pulmonary infections 1

High-Risk Groups for Chronic Q Fever:

• Patients with valvular heart disease 1
• Vascular graft recipients 1
• Arterial aneurysm patients 1
• Pregnant women 1
• Immunosuppressed individuals 1

Respiratory Causes:

• Upper airway cough syndrome (UACS) from rhinosinus conditions 1
• Asthma 1
• Gastroesophageal reflux disease (GERD) 1
• Nonasthmatic eosinophilic bronchitis 1
• Atopic cough (in Asian countries) 1

Non-Infectious Causes:

• Drug-induced fever (may take up to 21 days after administration to develop, 1-7 days to resolve after discontinuation) 3
• Malignant hyperthermia 3
• Neuroleptic malignant syndrome 3
• Serotonin syndrome 3

Undiagnosed Cases:

A significant portion of chronic fever cases remain undiagnosed despite thorough evaluation. 4

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Key Diagnostic Principles:

For Chronic Fever Workup:

• Obtain detailed history focusing on recent surgeries, immunocompromised status, drug exposures, and travel history 3
• Perform thorough physical examination 3
• Order basic laboratory tests including metabolic panel and liver function tests 3
• Consider imaging: chest radiography, CT for post-surgical patients, abdominal ultrasound for hepatobiliary symptoms 3
• For persistent fever of unknown origin, consider 18F-FDG PET/CT if transport risk is acceptable 3

Critical Pitfall: In 44% of patients with chronic fever, the final diagnosis comprises only six clinical entities: subacute thyroiditis, subacute endocarditis, Still's disease, rheumatic polymyalgia with or without temporal arteritis, and cytomegalovirus infection. 4 The diagnostic approach should always be directed toward the known frequency of diseases. 4