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Fever

Medicine > Cardiovascular

Differential Diagnosis Schema 🧠

Infective Causes

  • Viral Infections: Commonly include influenza, COVID-19, and infectious mononucleosis, often with associated symptoms like myalgia, sore throat, and cough.
  • Bacterial Infections: Pneumonia, urinary tract infections (UTIs), and bacterial meningitis typically present with high-grade fever, rigors, and localised symptoms.
  • Parasitic Infections: Malaria and dengue are key considerations in patients with a history of travel to endemic areas, presenting with fever, headache, and myalgia.
  • Fungal Infections: Consider in immunocompromised patients, such as those with HIV/AIDS or on immunosuppressive therapy, presenting with fever and non-specific symptoms.
  • Tuberculosis: Chronic low-grade fever, night sweats, weight loss, and cough, particularly in high-risk populations.
  • Sepsis: Systemic infection with evidence of organ dysfunction, often with fever, hypotension, and tachycardia.

Inflammatory and Autoimmune Causes

  • Systemic Lupus Erythematosus (SLE): Fever, malar rash, arthritis, and nephritis in a young female patient.
  • Rheumatoid Arthritis: Fever with joint pain and stiffness, particularly in the morning, along with evidence of synovitis.
  • Vasculitis: Systemic symptoms including fever, weight loss, and specific organ involvement such as renal impairment or pulmonary hemorrhage.
  • Inflammatory Bowel Disease: Fever with abdominal pain, diarrhoea, and weight loss, often with a history of Crohn’s disease or ulcerative colitis.
  • Sarcoidosis: Fever with non-caseating granulomas, pulmonary infiltrates, and erythema nodosum.
  • Adult-onset Still’s Disease: Daily fever spikes, salmon-colored rash, and arthritis.
  • Giant Cell Arteritis: Fever, headache, jaw claudication, and visual disturbances in an older patient.

Neoplastic Causes

  • Lymphoma: Fever, night sweats, weight loss, and lymphadenopathy; may present as Hodgkin’s or non-Hodgkin’s lymphoma.
  • Leukemia: Fatigue, recurrent infections, bruising, and fever, often with abnormal blood counts.
  • Solid Tumours: Fever can be a paraneoplastic phenomenon, particularly in renal cell carcinoma or hepatocellular carcinoma.
  • Metastatic Cancer: Fever due to tumour necrosis or secondary infection, especially in advanced cancer.
  • Multiple Myeloma: Recurrent infections, bone pain, anaemia, and fever in older adults.

Drug-Induced Causes

  • Drug Fever: Can occur with antibiotics (e.g., beta-lactams), anticonvulsants, or antiarrhythmics; resolves with drug withdrawal.
  • Neuroleptic Malignant Syndrome: Fever, rigidity, autonomic instability, and altered mental status in patients on antipsychotics.
  • Serotonin Syndrome: Hyperthermia, agitation, tremor, and hyperreflexia in patients on serotonergic drugs.
  • Malignant Hyperthermia: Sudden, life-threatening hyperthermia following exposure to anaesthetic agents in susceptible individuals.
  • Hypersensitivity Reactions: Fever, rash, eosinophilia, and systemic involvement (e.g., DRESS syndrome) with certain medications.

Key Points in History 🥼

Onset and Duration

  • Acute vs. Chronic: Acute fever is often due to infections or drug reactions, while chronic fever may suggest malignancy, tuberculosis, or autoimmune diseases.
  • Intermittent vs. Continuous: Intermittent fever (e.g., with malaria) may have different causes compared to continuous fever (e.g., in typhoid fever or lymphoma).
  • Pattern of Fever: Ask about diurnal variation (e.g., high fever in the evening), which may suggest certain infections or inflammatory conditions.
  • Response to Antipyretics: Lack of response to antipyretics may suggest non-infective causes such as malignancy or drug fever.

Associated Symptoms

  • Night Sweats: Common in lymphoma, tuberculosis, and endocarditis.
  • Weight Loss: Consider malignancy, tuberculosis, or chronic infections.
  • Rash: Suggests viral exanthems, drug reactions, or autoimmune conditions like SLE.
  • Arthralgia/Myalgia: May indicate viral infections, autoimmune diseases, or endocarditis.
  • Headache: Consider meningitis, encephalitis, or giant cell arteritis.
  • Cough and Haemoptysis: Raises suspicion for tuberculosis, pneumonia, or lung cancer.
  • Lymphadenopathy: Common in lymphoma, viral infections, and some autoimmune diseases.
  • Abdominal Pain: Consider intra-abdominal infections, liver disease, or malignancy.
  • Mental Status Changes: May indicate sepsis, encephalitis, or drug-induced causes like serotonin syndrome.
  • Travel History: Important for assessing risk of diseases like malaria, typhoid, or dengue.
  • Sexual History: Consider sexually transmitted infections like HIV, syphilis, or acute hepatitis.
  • Immunisation History: Consider in differential diagnosis, particularly with preventable infectious diseases.
  • Immunosuppression: History of HIV, chemotherapy, or immunosuppressive drugs may point towards opportunistic infections.

Background

  • Past Medical History: Look for chronic conditions that may predispose to infections or inflammatory diseases, such as diabetes, COPD, or autoimmune diseases.
  • Drug History: Review current and recent medications, especially antibiotics, antipsychotics, and new medications that could cause drug fever.
  • Family History: Ask about familial predisposition to autoimmune diseases, malignancies, or recurrent infections.
  • Social History: Assess for alcohol use, smoking, occupational exposures, or recent travel, which may influence differential diagnosis.
  • Vaccination History: Ensure up-to-date vaccinations, especially for preventable diseases like influenza, pneumococcal disease, and hepatitis B.
  • Sexual History: Assess for risk of sexually transmitted infections, including HIV, syphilis, and hepatitis.
  • Living Conditions: Assess for risk factors such as overcrowded housing or exposure to infectious diseases, particularly in immunocompromised patients.

Possible Investigations 🌡️

Blood Tests

  • Full Blood Count (FBC): To assess for leukocytosis (suggestive of bacterial infection), leukopenia (viral infections, sepsis), anaemia, and thrombocytopenia (e.g., in malaria).
  • C-Reactive Protein (CRP)/Erythrocyte Sedimentation Rate (ESR): Elevated in infections, inflammatory conditions, and malignancies.
  • Blood Cultures: Essential in cases of sepsis, endocarditis, and other serious infections to identify causative organisms.
  • Liver Function Tests (LFTs): May indicate hepatitis, sepsis, or other systemic infections with liver involvement.
  • Renal Function Tests: To assess for acute kidney injury in sepsis, dehydration, or nephrotoxic drug reactions.
  • Serum Lactate: Elevated in sepsis, tissue hypoperfusion, or severe infections, indicating poor prognosis.
  • Serum Ferritin: Elevated in infections, inflammation, or malignancy; particularly high in adult-onset Still’s disease.
  • Serology: Specific tests for HIV, hepatitis, EBV, CMV, and other infections based on clinical suspicion.
  • Procalcitonin: Elevated in bacterial infections, can help differentiate between bacterial and viral causes of fever.
  • Autoantibody Screen: Useful in diagnosing autoimmune conditions such as SLE, vasculitis, or rheumatoid arthritis.
  • Malaria Blood Smears: Essential in febrile patients with a history of travel to endemic areas.
  • Thyroid Function Tests: To assess for hyperthyroidism as a non-infectious cause of fever.
  • Bone Marrow Biopsy: Consider in cases of unexplained fever with pancytopenia or suspected hematological malignancy.

Imaging

  • Chest X-ray: First-line imaging for assessing pneumonia, tuberculosis, or other pulmonary causes of fever.
  • Abdominal Ultrasound: Useful for evaluating hepatosplenomegaly, abscesses, or gallbladder disease as causes of fever.
  • CT Scan: May be necessary to identify abscesses, malignancies, or other intra-abdominal pathology causing fever.
  • Echocardiogram: Essential in suspected endocarditis, particularly with new heart murmurs or positive blood cultures.
  • MRI: Useful in assessing suspected central nervous system infections or complications such as brain abscesses.
  • PET Scan: Consider in cases of fever of unknown origin, particularly if malignancy or hidden abscesses are suspected.

Microbiological Tests

  • Urine Culture: Essential in suspected urinary tract infections, especially in febrile patients.
  • Sputum Culture: Useful in patients with productive cough and fever, particularly when pneumonia or tuberculosis is suspected.
  • Lumbar Puncture: Indicated in suspected meningitis or encephalitis, with CSF analysis to determine the causative organism.
  • Throat Swab: For patients with sore throat and fever, particularly to identify streptococcal or viral causes.
  • Stool Culture: Indicated in patients with fever and diarrhoea to identify enteric pathogens.
  • Blood PCR: For rapid identification of certain pathogens such as Mycobacterium tuberculosis or viral infections like COVID-19.
  • Bone Marrow Culture: Consider in cases of unexplained fever with suspected disseminated infection or malignancy.
  • Skin Biopsy: Indicated in febrile patients with rash, to diagnose conditions like vasculitis, drug reactions, or infectious exanthems.

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Cardiovascular