Differential Diagnosis of Fever: A Comprehensive Guide for Clinicians

Introduction

Fever, an elevation in body temperature above the normal range, is a common and often perplexing clinical sign. While fever itself is a physiological response to illness, determining its underlying cause is crucial for effective patient management. The process of identifying the specific etiology of a fever is known as differential diagnosis. This article provides a comprehensive guide to the Differential Diagnosis Of Fever, aiming to enhance clinical reasoning and improve patient outcomes. Understanding the diverse causes of fever, from common infections to rare inflammatory conditions and malignancies, is essential for healthcare professionals. This guide builds upon the foundations of fever of unknown origin (FUO) investigation, expanding the scope to encompass a broader spectrum of febrile illnesses and diagnostic strategies.

Understanding Fever

Fever is defined as a body temperature greater than the normal range, typically considered to be above 100.4°F (38°C) when measured orally. Normal body temperature varies slightly throughout the day and is influenced by factors such as age, activity level, and time of day. Fever is a regulated rise in body temperature mediated by the hypothalamus in response to pyrogens. These pyrogens can be exogenous, such as bacterial toxins, or endogenous, such as cytokines released by immune cells during infection or inflammation. The body’s thermoregulatory set point is elevated, leading to heat generation and conservation mechanisms like shivering and vasoconstriction to reach the new set point.

Initial Assessment and History Taking

A detailed history and thorough physical examination are paramount in narrowing the differential diagnosis of fever. The initial assessment should focus on gathering comprehensive information to guide subsequent investigations.

Key Historical Aspects:

• Detailed Symptom Analysis: Beyond fever, inquire about associated symptoms such as chills, sweats, fatigue, weight loss, pain (location, type), cough, rash, gastrointestinal symptoms, neurological changes, and urinary symptoms. The constellation of symptoms can significantly narrow the diagnostic possibilities.
• Past Medical History: Document pre-existing conditions, including chronic illnesses (diabetes, autoimmune diseases, heart conditions), previous infections (tuberculosis, HIV), surgeries, and hospitalizations.
• Medication History: Obtain a complete list of all medications, including prescription drugs, over-the-counter medications, herbal supplements, and illicit substances. Drug fever is a significant consideration in differential diagnosis.
• Travel History: Detailed travel history is crucial, especially for patients presenting with fever after returning from endemic regions. Inquire about destinations, duration of travel, activities, food and water sources, insect bites, and vaccinations.
• Occupational and Environmental Exposures: Explore occupational risks and environmental exposures, including contact with animals, exposure to toxins, and potential infectious agents in the workplace or home environment.
• Social History: Gather information about lifestyle factors such as smoking, alcohol consumption, sexual history, and recreational drug use, as these can predispose individuals to certain infections or conditions.
• Family History: Inquire about family history of fever syndromes, autoimmune diseases, malignancies, and infectious diseases to identify potential genetic predispositions or familial patterns.
• Immunization History: Review immunization records to assess protection against vaccine-preventable diseases that can present with fever.
• Dental History: Dental infections can be a source of fever and systemic illness, especially in cases of endocarditis.
• Animal Contacts: Document any contact with animals, including pets, farm animals, and wild animals, as zoonotic infections are important considerations.

Key Physical Examination Aspects:

A comprehensive physical examination is essential to identify clinical clues that can guide the differential diagnosis.

• Vital Signs: Accurate measurement of temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation is fundamental. Note any discrepancies or patterns, such as relative bradycardia in the context of fever (suggestive of typhoid fever, drug fever, or certain infections).
• General Appearance: Assess the patient’s overall appearance, level of consciousness, and signs of distress.
• Skin Examination: Carefully examine the skin for rashes (macular, papular, vesicular, petechial, purpuric), lesions, ulcers, or signs of infection (cellulitis, abscess). The characteristics and distribution of rashes are often diagnostically helpful.
• Head, Eyes, Ears, Nose, and Throat (HEENT): Examine the head and neck for signs of infection (sinusitis, otitis media, pharyngitis, tonsillitis), lymphadenopathy, and thyroid abnormalities.
• Cardiovascular Examination: Auscultate the heart for murmurs, rubs, or gallops, which may suggest endocarditis or other cardiac conditions.
• Respiratory Examination: Assess lung sounds for abnormalities such as crackles, wheezes, or decreased breath sounds, indicative of pneumonia, bronchitis, or pleural effusion.
• Abdominal Examination: Palpate the abdomen for tenderness, organomegaly (hepatomegaly, splenomegaly), masses, or signs of peritonitis.
• Neurological Examination: Assess mental status, cranial nerves, motor and sensory function, reflexes, and meningeal signs (nuchal rigidity) to evaluate for central nervous system infections or neurological disorders.
• Musculoskeletal Examination: Examine joints for swelling, tenderness, erythema, and range of motion limitations, which may suggest rheumatologic conditions or septic arthritis.
• Lymph Node Examination: Palpate lymph nodes in all regions (cervical, axillary, inguinal, supraclavicular) for size, consistency, tenderness, and mobility, which can be indicative of infection, malignancy, or inflammatory conditions.

By combining a detailed history with a thorough physical examination, clinicians can generate a more focused differential diagnosis and guide targeted investigations.

Categorizing Fever Etiologies

The differential diagnosis of fever is broad, but it can be systematically categorized into major etiological groups: infections, inflammatory conditions, neoplasms, and miscellaneous causes.

Infectious Causes of Fever

Infections remain the most common cause of fever. The spectrum of infectious agents is vast, including bacteria, viruses, fungi, parasites, and mycobacteria.

Bacterial Infections:

• Localized Infections:
  • Respiratory Tract Infections: Pneumonia (bacterial, atypical), bronchitis, sinusitis, otitis media, tonsillitis, epiglottitis.
  • Urinary Tract Infections (UTIs): Cystitis, pyelonephritis, prostatitis.
  • Skin and Soft Tissue Infections: Cellulitis, erysipelas, abscesses, wound infections.
  • Intra-abdominal Infections: Appendicitis, cholecystitis, diverticulitis, peritonitis, liver abscess, splenic abscess, psoas abscess.
  • Bone and Joint Infections: Osteomyelitis, septic arthritis, discitis.
  • Central Nervous System (CNS) Infections: Meningitis (bacterial), encephalitis, brain abscess.
• Systemic Infections:
  • Sepsis: Systemic inflammatory response syndrome (SIRS) due to infection.
  • Bacteremia: Presence of bacteria in the bloodstream.
  • Endocarditis: Infection of the heart valves.
  • Typhoid Fever (Enteric Fever): Salmonella typhi infection, often associated with travel to endemic areas.
  • Brucellosis: Brucella species infection, often linked to consumption of unpasteurized dairy products or animal contact.
  • Tuberculosis (TB): Mycobacterium tuberculosis infection, can be pulmonary or extrapulmonary (miliary TB, lymphatic TB, CNS TB).
  • Q Fever: Coxiella burnetii infection, often associated with farm animals, particularly sheep and goats.
  • Leptospirosis: Leptospira species infection, transmitted through contact with contaminated water or animal urine.
  • Cat Scratch Disease: Bartonella henselae infection, following a cat scratch or bite.
  • Lyme Disease: Borrelia burgdorferi infection, transmitted by tick bites.
  • Tick-borne Relapsing Fever: Borrelia recurrentis infection, transmitted by ticks or lice.
  • Rat-bite Fever: Streptobacillus moniliformis or Spirillum minus infection, following a rat bite.

Viral Infections:

• Common Viral Infections: Influenza, common cold (rhinovirus, coronavirus), adenovirus infections.
• Exanthematous Viral Infections: Measles, rubella, varicella (chickenpox), roseola infantum (sixth disease), erythema infectiosum (fifth disease).
• Enteroviral Infections: Coxsackievirus, echovirus infections, can cause fever, rash, herpangina, hand-foot-and-mouth disease, aseptic meningitis.
• Epstein-Barr Virus (EBV) Infection (Infectious Mononucleosis): Fever, pharyngitis, lymphadenopathy, fatigue.
• Cytomegalovirus (CMV) Infection: Often asymptomatic in immunocompetent individuals, but can cause fever, mononucleosis-like syndrome, or organ-specific disease in immunocompromised patients.
• HIV Infection: Acute retroviral syndrome can present with fever, rash, lymphadenopathy, and flu-like symptoms. Opportunistic infections in later stages of HIV can also cause fever.
• Hepatitis (Viral): Hepatitis A, B, C, D, E can present with fever, jaundice, fatigue, and abdominal pain.
• Arboviral Infections: Dengue fever, Zika virus, chikungunya, West Nile virus, transmitted by mosquitoes.
• Hantavirus Infections: Hantavirus pulmonary syndrome (HPS), hemorrhagic fever with renal syndrome (HFRS), transmitted by rodent exposure.

Fungal Infections:

• Invasive Fungal Infections: Candida species, Aspergillus species, Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Pneumocystis jirovecii. More common in immunocompromised individuals.
• Localized Fungal Infections: Less likely to cause systemic fever unless disseminated.

Parasitic Infections:

• Malaria: Plasmodium species infection, transmitted by mosquito bites, characterized by cyclical fevers, chills, and sweats.
• Amebiasis: Entamoeba histolytica infection, can cause liver abscess and fever.
• Toxoplasmosis: Toxoplasma gondii infection, often asymptomatic, but can cause fever, lymphadenopathy, and CNS involvement, especially in immunocompromised individuals and pregnant women.
• Leishmaniasis: Leishmania species infection, transmitted by sandflies, can be visceral (kala-azar) with fever, hepatosplenomegaly, and pancytopenia.
• Babesiosis: Babesia species infection, transmitted by tick bites, can cause fever, hemolytic anemia, and flu-like symptoms.
• Chagas Disease: Trypanosoma cruzi infection, transmitted by reduviid bugs, acute phase can present with fever and local inflammation.

Mycobacterial Infections:

• Tuberculosis (TB): Mycobacterium tuberculosis infection (discussed above under bacterial infections).
• Atypical Mycobacterial Infections: Mycobacterium avium complex (MAC), Mycobacterium kansasii, Mycobacterium marinum, etc. Can cause pulmonary disease, disseminated infection, lymphadenitis, skin infections, especially in immunocompromised individuals.

Inflammatory and Autoimmune Causes of Fever

Non-infectious inflammatory conditions and autoimmune diseases are significant causes of fever, particularly in developed countries.

• Rheumatologic Diseases:

  • Adult-Onset Still’s Disease: High spiking fevers, arthritis, evanescent salmon-colored rash, sore throat, elevated ferritin.
  • Systemic Lupus Erythematosus (SLE): Fever, fatigue, arthritis, rash (malar rash), serositis, renal involvement, neurological manifestations.
  • Rheumatoid Arthritis (RA): Fever (less common as primary presentation), joint pain and swelling, morning stiffness, systemic symptoms.
  • Polymyalgia Rheumatica (PMR): Fever, muscle pain and stiffness (shoulders, hips), elevated ESR/CRP, often associated with giant cell arteritis.
  • Giant Cell Arteritis (Temporal Arteritis): Fever, headache, temporal artery tenderness, jaw claudication, visual disturbances, elevated ESR/CRP.
  • Vasculitides: Periarteritis nodosa, microscopic polyangiitis, granulomatosis with polyangiitis (Wegener’s), eosinophilic granulomatosis with polyangiitis (Churg-Strauss), Takayasu arteritis, Behçet’s disease. Fever, systemic symptoms, and organ-specific manifestations depending on the type of vasculitis.
  • Sarcoidosis: Fever, fatigue, cough, dyspnea, lymphadenopathy, erythema nodosum, uveitis, multiorgan involvement.
  • Reactive Arthritis (Reiter’s Syndrome): Fever, arthritis, conjunctivitis, urethritis, often triggered by infection (e.g., Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter).
  • Inflammatory Bowel Disease (IBD): Crohn’s disease, ulcerative colitis. Fever, abdominal pain, diarrhea, weight loss, extraintestinal manifestations.

• Autoinflammatory Syndromes:

  • Familial Mediterranean Fever (FMF): Recurrent episodes of fever, serositis (abdominal pain, pleuritic chest pain), arthritis, erysipelas-like rash, common in individuals of Mediterranean descent.
  • Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS): Recurrent fevers, abdominal pain, myalgia, periorbital edema, rash, prolonged attacks lasting weeks.
  • Hyperimmunoglobulinemia D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD): Recurrent fevers, lymphadenopathy, abdominal pain, diarrhea, rash, aphthous ulcers.
  • Cryopyrin-Associated Periodic Syndromes (CAPS): Includes familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular (CINCA) syndrome. Variable presentations with fever, rash, arthralgia, and systemic inflammation.
  • Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome: Recurrent periodic fevers, pharyngitis, aphthous ulcers, cervical lymphadenitis in children.

• Other Inflammatory Conditions:

  • Gout and Pseudogout: Crystal-induced arthropathies, acute attacks can present with fever and joint inflammation.
  • Pancreatitis: Inflammation of the pancreas, can cause fever, abdominal pain, nausea, vomiting.
  • Thyroiditis (Subacute Thyroiditis/de Quervain’s Thyroiditis): Inflammation of the thyroid gland, can cause fever, neck pain, tender thyroid, hyperthyroidism followed by hypothyroidism.
  • Sarcoidosis: (Also listed under rheumatologic, but can be considered broadly inflammatory).

Neoplastic Causes of Fever

Malignancies can cause fever through various mechanisms, including cytokine release, tumor necrosis, and secondary infections.

• Hematologic Malignancies:

  • Lymphoma (Hodgkin and Non-Hodgkin): Fever (Pel-Ebstein fever in Hodgkin lymphoma), night sweats, weight loss, lymphadenopathy, fatigue.
  • Leukemia (Acute and Chronic): Fever, fatigue, bleeding, infections, bone pain, lymphadenopathy, splenomegaly.
  • Myeloproliferative Neoplasms: Polycythemia vera, essential thrombocythemia, primary myelofibrosis. Fever, night sweats, weight loss, splenomegaly, thrombocytosis or erythrocytosis.
  • Multiple Myeloma: Fever (less common), bone pain, fatigue, hypercalcemia, renal insufficiency, anemia.
  • Myelodysplastic Syndromes (MDS): Fever (due to infections), fatigue, cytopenias.

• Solid Tumors:

  • Renal Cell Carcinoma: Fever, flank pain, hematuria, weight loss, palpable mass.
  • Hepatocellular Carcinoma (Hepatoma): Fever, abdominal pain, jaundice, weight loss, ascites.
  • Pancreatic Cancer: Fever, abdominal pain, jaundice, weight loss, diabetes.
  • Colon Cancer: Fever (less common, especially in advanced stages), change in bowel habits, abdominal pain, rectal bleeding, weight loss.
  • Lung Cancer: Fever, cough, hemoptysis, chest pain, weight loss, dyspnea.
  • Breast Cancer: Fever (less common unless metastatic), breast mass, skin changes, nipple discharge.
  • Atrial Myxoma: Benign tumor of the heart, can cause fever, constitutional symptoms, embolic events, cardiac murmurs.
  • Metastatic Cancer: Fever can be a manifestation of widespread metastases, particularly to the liver or bone.

Miscellaneous Causes of Fever

This category encompasses a variety of less common or atypical causes of fever.

• Drug Fever: Fever caused by medications, can occur with many drug classes. Beta-lactam antibiotics, sulfonamides, phenytoin, allopurinol, and procainamide are common culprits. Discontinuation of the drug typically resolves the fever.
• Central Fever: Fever due to hypothalamic dysfunction, often associated with CNS trauma, surgery, or stroke. Characterized by high fever, lack of diurnal variation, and resistance to antipyretics.
• Factitious Fever: Self-induced fever, often seen in individuals with psychological disorders. May involve manipulation of thermometers.
• Hyperthermia: Unregulated increase in body temperature due to external heat exposure or excessive heat production (e.g., heat stroke, malignant hyperthermia). Different from fever as it does not involve a change in the hypothalamic set point.
• Pulmonary Embolism (PE): Fever, chest pain, dyspnea, hemoptysis, risk factors for thromboembolism.
• Deep Vein Thrombosis (DVT): Fever, leg pain and swelling, risk factors for thromboembolism.
• Hematoma: Large hematomas can sometimes cause low-grade fever.
• Cirrhosis: Liver cirrhosis, particularly with portal hypertension and bacterial translocation, can cause low-grade fever.
• Hypothyroidism and Hyperthyroidism (Thyroid Storm): While thyroid disorders primarily affect thermoregulation, thyroid storm (severe hyperthyroidism) can present with high fever. Hypothyroidism can sometimes cause mild temperature dysregulation.
• Cyclic Neutropenia: Periodic decreases in neutrophil count, leading to recurrent fevers and infections.
• Hypertriglyceridemia (Type V Hyperlipoproteinemia): Rarely, severe hypertriglyceridemia can be associated with fever and abdominal pain.
• Subacute Thyroiditis (de Quervain’s Thyroiditis): (Also listed under inflammatory, but has endocrine aspects).

Diagnostic Approach to Fever

The diagnostic approach to fever involves a systematic and stepwise process, guided by the clinical presentation and initial investigations.

Initial Investigations (Non-invasive Tests):

These tests are typically performed early in the evaluation of fever to screen for common causes and provide baseline data.

• Complete Blood Count (CBC) with Differential: Evaluates white blood cell count (leukocytosis, leukopenia), differential (neutrophilia, lymphocytosis, eosinophilia), hemoglobin, and platelets. Can suggest infection, inflammation, hematologic malignancy, or bone marrow suppression.
• Complete Metabolic Panel (CMP): Assesses electrolytes, renal function (BUN, creatinine), liver function tests (AST, ALT, bilirubin, alkaline phosphatase), and glucose. Can detect liver disease, renal disease, electrolyte imbalances, and metabolic disorders.
• Urinalysis with Microscopy and Urine Culture: Detects urinary tract infection, hematuria, proteinuria, and casts.
• Blood Cultures (Three Sets): Obtained from different sites and at different times to maximize yield. Essential for diagnosing bacteremia, sepsis, and endocarditis. Should ideally be drawn before antibiotic administration.
• Chest Radiograph: Screens for pneumonia, tuberculosis, lung abscess, pleural effusion, and mediastinal masses.
• Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Markers of inflammation, elevated in infections, inflammatory conditions, and malignancies. Non-specific but can indicate the presence and degree of inflammation.
• Lactate Dehydrogenase (LDH) and Creatine Phosphokinase (CPK): LDH can be elevated in various conditions including hemolysis, tissue injury, and certain malignancies. CPK is elevated in muscle injury, rhabdomyolysis, and myocardial infarction.
• Antinuclear Antibodies (ANA) and Rheumatoid Factor (RF): Screening tests for autoimmune diseases like SLE and RA. Positive results require further evaluation.
• Cytomegalovirus (CMV) IgM/PCR and Heterophile Antibody Test (Monospot): Used to diagnose acute CMV and Epstein-Barr virus (EBV) infections, respectively.
• Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA): Tests for latent tuberculosis infection.
• HIV Immunoassay: Screening test for HIV infection, particularly important in patients with risk factors or unexplained fever.
• Computed Tomography (CT) Scan of the Chest, Abdomen, and Pelvis: Useful for detecting abscesses, tumors, lymphadenopathy, organomegaly, and inflammatory processes in the chest, abdomen, and pelvis. Guided by clinical suspicion and initial findings.
• Echocardiography: Transthoracic or transesophageal echocardiography to evaluate for endocarditis, particularly in cases of persistent fever and new heart murmur.

Advanced Investigations (Invasive and Specialized Tests):

These tests are considered when initial non-invasive investigations are inconclusive or when clinical suspicion for specific conditions is high.

• Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT): Highly sensitive for detecting areas of increased metabolic activity, suggestive of infection, inflammation, or malignancy. Useful in FUO workup to guide further investigations, but not specific.
• Labeled Leukocyte Scan (Gallium or Indium): Nuclear medicine scans that use radiolabeled leukocytes to localize sites of infection or inflammation. Less specific than FDG-PET/CT but can be helpful when PET/CT is not available.
• Biopsies: Guided biopsies of lymph nodes, liver, bone marrow, skin lesions, or temporal artery (temporal artery biopsy for giant cell arteritis) may be necessary to obtain tissue for histopathological examination, culture, and special stains to diagnose malignancy, infections (e.g., tuberculosis, fungal infections), or inflammatory conditions.
• Bone Marrow Aspiration and Biopsy: Indicated in cases of suspected hematologic malignancy, disseminated infection, or unexplained cytopenias.
• Lumbar Puncture (Spinal Tap): To evaluate cerebrospinal fluid (CSF) in cases of suspected meningitis, encephalitis, or CNS involvement.
• Endoscopy (Upper and Lower Gastrointestinal Endoscopy, Colonoscopy): To evaluate for gastrointestinal sources of fever, such as inflammatory bowel disease, infections, or tumors. May include biopsies of the gastrointestinal tract.
• Bronchoscopy with Bronchoalveolar Lavage (BAL): To evaluate for pulmonary infections or inflammatory conditions, particularly in immunocompromised patients or those with suspected atypical pneumonia.
• Laparoscopy or Laparotomy: In rare cases of persistent FUO without a diagnosis, exploratory laparoscopy or laparotomy may be considered to identify intra-abdominal pathology.
• Specialized Serological and Molecular Tests: Depending on the clinical suspicion, specific serological tests for viral infections, rickettsial infections, Lyme disease, or molecular tests (PCR) for specific pathogens may be indicated.

Empirical Therapy:

Empirical antibiotic therapy is generally not recommended in the initial management of fever unless there is strong clinical suspicion of bacterial sepsis or neutropenic fever. Indiscriminate use of antibiotics can mask underlying infections, delay diagnosis, and contribute to antibiotic resistance.

In certain specific situations, empirical therapy may be considered:

• Neutropenic Fever: Febrile neutropenia is a medical emergency, and empirical broad-spectrum antibiotics should be initiated promptly.
• Suspected Sepsis: In cases of clinically suspected sepsis with hemodynamic instability, empirical antibiotics are warranted after obtaining blood cultures.
• Specific Syndromes: In certain clinical syndromes with high pretest probability of specific infections (e.g., suspected bacterial meningitis, community-acquired pneumonia in certain settings), empirical therapy may be initiated while awaiting diagnostic results.

Empirical glucocorticoids are also generally not recommended unless there is a strong suspicion for a specific rheumatologic condition (e.g., temporal arteritis with vision loss) or life-threatening inflammatory condition.

Observation and Follow-up:

In some cases of fever, particularly if the patient is stable and the etiology is unclear after initial investigations, a period of observation with close follow-up may be appropriate. Serial physical examinations, repeat laboratory tests, and imaging may be necessary to monitor the clinical course and identify evolving diagnostic clues.

Differential Diagnosis in Specific Clinical Scenarios

The differential diagnosis of fever can be further refined by considering specific clinical scenarios and associated symptoms.

• Fever with Rash: Consider viral exanthems (measles, rubella, varicella, roseola, erythema infectiosum, enteroviral infections), drug eruptions, bacterial infections (scarlet fever, toxic shock syndrome, meningococcemia, secondary syphilis, Lyme disease), rheumatologic diseases (SLE, adult Still’s disease, vasculitis), and autoinflammatory syndromes.
• Fever with Cough: Consider respiratory tract infections (pneumonia, bronchitis, influenza, pertussis, tuberculosis), lung abscess, empyema, and less commonly, pulmonary embolism or lung cancer.
• Fever with Abdominal Pain: Consider intra-abdominal infections (appendicitis, cholecystitis, diverticulitis, peritonitis, liver abscess, splenic abscess, psoas abscess), inflammatory bowel disease, pancreatitis, hepatitis, and less commonly, renal cell carcinoma or lymphoma.
• Fever in Immunocompromised Patients: The differential diagnosis is broader and includes opportunistic infections (Pneumocystis pneumonia, CMV, Mycobacterium avium complex, fungal infections, toxoplasmosis), bacterial infections, viral infections, drug fever, and malignancy.
• Fever in Travelers: Consider travel-related infections such as malaria, typhoid fever, dengue fever, Zika virus, chikungunya, rickettsial infections, leishmaniasis, amebic liver abscess, and tuberculosis.

Conclusion

The differential diagnosis of fever is a complex and challenging clinical endeavor. A systematic approach that integrates a detailed history, thorough physical examination, and judicious use of diagnostic investigations is essential for accurate diagnosis and effective management. Categorizing fever etiologies into infectious, inflammatory, neoplastic, and miscellaneous causes provides a useful framework for clinical reasoning. While infections remain the most common cause of fever, non-infectious conditions and malignancies should also be carefully considered, particularly in cases of persistent or unexplained fever. By utilizing a comprehensive and thoughtful diagnostic approach, clinicians can effectively navigate the differential diagnosis of fever and improve patient outcomes.

References

The references from the original article are relevant and comprehensive for the topic of fever and FUO, and are retained here for this expanded article on differential diagnosis of fever.

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