Types of Fever: Classification by Pattern and Underlying Cause
Fever is classified into four primary clinical categories based on duration and patient context—classical, nosocomial, neutropenic, and HIV-related fever of unknown origin—with additional classification by temporal patterns and underlying etiologies that guide diagnostic and therapeutic approaches. 1, 2
Classification by Clinical Context
Primary Categories of Fever of Unknown Origin (FUO)
The most clinically relevant classification system divides fever into four distinct subcategories based on patient population and setting:
Classical FUO: Fever exceeding 38.3°C (100.9°F) persisting for at least 3 weeks without diagnosis despite 3 outpatient visits or in-patient days in immunocompetent patients 1, 2
Nosocomial FUO: Fever developing in hospitalized patients without infection present on admission, persisting without diagnosis despite appropriate investigation 1, 2
Neutropenic FUO: Fever in patients with absolute neutrophil count <500 cells/µL, defined as either a single oral temperature ≥38.3°C OR ≥38.0°C sustained over at least 1 hour—notably a lower threshold than classical FUO 1, 2
HIV-related FUO: Fever in HIV-positive patients persisting for more than 3 weeks as an outpatient or more than 3 days as an inpatient without identified cause 1, 2
This classification is critical because etiology distribution varies significantly by category and geographic location, fundamentally altering the diagnostic approach and empirical treatment decisions. 1
Classification by Temporal Fever Patterns
Historical Fever Pattern Recognition
While classical fever patterns based on recordings every 8-12 hours have been developed historically, these patterns do not provide meaningful information in diagnosing diseases in modern clinical practice. 3 However, understanding these patterns remains relevant for recognizing specific syndromes:
Continuous fever: Persistent elevation with minimal variation (<1°C daily fluctuation) 4
Intermittent fever: Temperature returns to normal daily, with marked diurnal variation 4
Remittent fever: Daily fluctuations >1°C but temperature does not return to normal 4
Relapsing/recurrent fever: Febrile periods separated by afebrile intervals of days to weeks 4
The clinical significance of these patterns has diminished with modern diagnostic capabilities, though certain patterns may still suggest specific etiologies (e.g., tertian or quartan patterns in malaria). 4
Classification by Underlying Etiology
Infectious Causes
Respiratory infections are the predominant cause of acute fever, with viral pathogens being most common, followed by bacterial pneumonia and exacerbations of underlying lung disease. 5
Key infectious etiologies include:
Bacterial infections: Endocarditis (comprising 60-78% of chronic Q fever cases and invariably fatal if untreated), pneumonia, urinary tract infections, and device-related infections (30-40% of S. aureus bacteremia cases involve cardiac devices) 5
Tropical diseases in returning travelers: Malaria (92% present with fever), dengue (78% present with fever), enteric fever (82% present with fever), and rickettsioses (88% present with fever) 6
Parasitic infections: Intestinal helminths, schistosomiasis, strongyloidiasis, and filariasis, particularly in travelers 5
Opportunistic infections: Systemic candidiasis and Pneumocystis jiroveci pneumonia in immunocompromised patients 7
Non-Infectious Causes
Two life-threatening hyperthermic syndromes require immediate recognition: malignant hyperthermia (caused by succinylcholine and inhalation anesthetics, mediated by dysregulation of cytoplasmic calcium in skeletal muscle) and neuroleptic malignant syndrome (associated with antipsychotic medications, particularly haloperidol in ICU settings). 6
Additional non-infectious etiologies include:
Malignancy-related fever: Paraneoplastic syndromes, tumor necrosis, or hematologic malignancies (hepatosplenomegaly in FUO may indicate lymphoma) 5, 7
Drug-induced fever: Can occur with mean lag time of 21 days (median 8 days) after drug initiation, taking 1-7 days to resolve after discontinuation; rash and eosinophilia are uncommon 6
Rheumatic/autoimmune conditions: Adult-onset Still's disease, rheumatic fever (requires 2 major or 1 major plus 2 minor criteria with evidence of preceding streptococcal infection) 6, 5
Thromboembolic disease: Venous thromboembolism is a common cause in cancer patients 7
Endocrine causes: Thyroid storm must be excluded in FUO workup 5
Special Population Considerations
Long-Term Care Facility Residents
In frail elderly populations, basal body temperatures may be lower than 37°C (98.6°F), requiring adjusted fever criteria: a single temperature ≥37.8°C (100°F) has 70% sensitivity and 90% specificity for predicting infection, or alternatively, an increase of ≥1.1°C (2°F) over baseline. 6
Tachypnea >25 breaths/min has 90% sensitivity and 95% specificity for pneumonia diagnosis in LTCF residents, with positive and negative predictive values of 95%. 6
Returning Travelers and Migrants
Geographic-specific risk stratification is essential: Central/Western Africa suggests malaria, while Eastern/Western Africa suggests dengue and schistosomiasis. 1 Patients visiting friends and relatives are less likely to seek pre-travel advice and have higher malaria rates. 1
Critically Ill ICU Patients
The Society of Critical Care Medicine defines fever as a single temperature ≥38.3°C (100.9°F) without the 3-week duration requirement for diagnostic purposes in ICU patients. 1 Central temperature monitoring via pulmonary artery catheter, bladder catheters, or esophageal balloon thermistors is preferred; axillary, tympanic, temporal artery, or chemical dot thermometers should not be used due to unreliability. 1
Critical Diagnostic Patterns
High-Yield Clinical Predictors
Q fever pattern: Prolonged fever (>10 days) with normal leukocyte count, thrombocytopenia, and elevated liver enzymes strongly suggests Q fever 5
Normal WBC does not exclude infection: Up to 75% of patients with prolonged fever have normal white blood cell counts 5
Fever with new heart murmur or heart failure signs: Consider endocarditis until proven otherwise 5
Persistent fever >5-7 days despite appropriate antibiotics: Suggests abscess formation, resistant organisms, or need for surgical intervention 5
Common Pitfalls to Avoid
Never initiate empirical antibiotics without obtaining at least 3 sets of blood cultures first—this is the major cause of culture-negative infections and obscures diagnosis. 5, 2
Do not assume normal WBC excludes infection, as leukocyte count is normal in up to 75% of prolonged fever cases. 5
Fever may be absent in elderly and immunocompromised patients despite serious infection, so normal temperatures do not exclude infection—absence of fever in infected patients is associated with worse outcomes. 1, 5
Avoid empiric steroids in stable FUO patients, as they obscure diagnosis, mask inflammatory findings on subsequent imaging, and increase risks of hospital-acquired infection, hyperglycemia, gastrointestinal bleeding, and delirium without improving mortality. 1, 5