Makindo Medical Notes

Related Subjects: | Fever in a Traveller | Malaria Falciparum | Malaria Non Falciparum | Viral Haemorrhagic Fevers (VHF) | Lassa Fever | Dengue | Marburg Virus Disease | AIDS/HIV | Yellow Fever | Ebola Virus | Leptospirosis | Crimean-Congo Haemorrhagic Fever | African Trypanosomiasis (Sleeping Sickness) | American Trypanosomiasis (Chagas Disease) | Incubation Periods | Notifiable Diseases UK

🌡️ Key Point: FUO requires multiple expert opinions because causes are broad, and not all prolonged fevers are infectious. Current definition: Documented fever persisting >2 weeks with no clear diagnosis despite thorough and directed investigation.

📖 About

• Original (Petersdorf & Beeson, 1960s): Temp >38.3 °C for >3 weeks with no diagnosis after 1 week of inpatient work-up (pre-CT/MRI era).
• Current: Fever >2 weeks with no diagnosis despite detailed investigations.
• Fever = cytokines/interferons reset hypothalamic set point. 🚨 May be absent in elderly, steroid-treated, or immunocompromised patients.
• Any pyrogen (microbial toxin, cytokine, necrotic material) can trigger fever.

🧾 Definitions

• Current: >2 weeks, unexplained after thorough testing.
• Original: >38 °C, >3 weeks, unexplained after 1 week hospital investigations.

🩺 Differential Diagnoses

• Infections: TB, endocarditis, urinary/resp tract infections.
• Abscesses: Pelvic, renal, epidural, subdiaphragmatic.
• Tropical/Parasitic: Malaria, amoebiasis, leishmaniasis, trypanosomiasis.
• Other infections: EBV/CMV, brucellosis, HIV, Lyme, Whipple’s, rickettsiae.
• Rheumatological: GCA, PMR, SLE, Still’s, vasculitides.
• Genetic: Familial Mediterranean Fever.
• Malignancy: Lymphoma, leukaemia, renal cell carcinoma, solid tumours.
• Other: Drug fever, atrial myxoma, thyrotoxicosis.

🔑 Key Clinical Approaches

• 🧳 History: travel, drug use (esp. IV), occupational & sexual exposures.
• 👀 Exam: skin, oral/dental, lymph nodes, rectal/pelvic where indicated.
• 📸 Imaging: chest X-ray, ultrasound, CT/MRI → hidden abscess/malignancy.
• 🔁 Re-evaluate: repeat history/exam frequently; new clues often evolve.
• 🤝 Seek early specialist input: rheumatology, haematology, microbiology, cardiology.

🔬 Investigations

• Basic labs: FBC, ESR/CRP, LFTs, U&Es, TFTs.
• Serology: EBV, CMV, HIV, Bartonella, Toxoplasma, Brucella, Lyme, Q fever.
• Microbiology: Blood, urine, stool cultures (≥3 sets); wound swabs if relevant.
• Imaging: CXR, abdo/pelvic US, CT, MRI. Consider bone/WBC-labelled scans.
• Specialised: Echocardiogram (endocarditis/myxoma), malaria films (×3), autoimmune panels (ANA, ANCA, RF).
• Biopsy: Liver (TB, lymphoma, granulomas), bone marrow (malignancy, leishmaniasis, TB), temporal artery (>50yrs, rule out GCA).

📊 Causes of FUO

Category	Examples / Notes
🦠 Common Infections (30–40%)	UTI, chest infections, endocarditis. Take blood cultures before antibiotics.
🦟 Malaria	Travel history vital. Falciparum malaria = rapidly fatal. Do thick & thin films.
🧫 Tuberculosis	Miliary/extrapulmonary. May need CXR, IGRA, biopsy.
💥 Abscess	Splenic, perirenal, pelvic, spinal. Requires CT/US/MRI for localisation.
🧬 Other Infections	HIV, osteomyelitis, typhoid, brucellosis, Lyme, EBV, CMV, Bartonella, toxoplasmosis.
🎗️ Malignancy (~20%)	Lymphoma, leukaemia, renal cell carcinoma. Often ↑ESR/LDH.
🔥 Inflammatory (10–20%)	GCA, Still’s, SLE, vasculitis, RA. Very high ESR in GCA.
⚖️ Miscellaneous	Atrial myxoma, sarcoidosis, Crohn’s, FMF, occult haematoma, thyrotoxicosis.
❓ Idiopathic	No diagnosis despite extensive work-up.
💊 Drugs	Drug-induced fever; thorough med history crucial.
🕵️ Factitious	Deliberate fever. Normal ESR/CRP. Check fresh urine temp to confirm.

🧑‍⚕️ Management Principles

• 🚫 Avoid “blind” antibiotics — they obscure cultures & mask clues.
• ✅ Re-evaluate regularly; revisit history & exam with fresh eyes.
• 🤝 Discuss with seniors & specialists early (multidisciplinary approach).
• 📅 Stable outpatients: follow up carefully; unstable patients → urgent admission.
• 💊 Suspend unnecessary meds to rule out drug fever.

Cases — Pyrexia of Unknown Origin (PUO / FUO)

• Case 1 — Infective (Tuberculosis): A 35-year-old man presents with 6 weeks of intermittent fever, night sweats, and weight loss. No cough. CXR: miliary mottling. ESR raised, Quantiferon positive. Diagnosis: Disseminated tuberculosis. Management: Anti-TB therapy (RIPE regimen), prolonged course; notify public health.
• Case 2 — Infective (Endocarditis): A 52-year-old man with a prosthetic mitral valve presents with 5 weeks of low-grade fever, sweats, and weight loss. Exam: new murmur, splinter haemorrhages. Blood cultures: *Streptococcus viridans*. Echo: vegetation. Diagnosis: Infective endocarditis. Management: Prolonged IV antibiotics ± surgery if refractory or valve destruction.
• Case 3 — Malignancy (Lymphoma): A 42-year-old woman has 2 months of fever, drenching night sweats, and weight loss. Exam: cervical lymphadenopathy, splenomegaly. LDH high. Node biopsy: Reed–Sternberg cells. Diagnosis: Hodgkin lymphoma. Management: Staging and chemotherapy (ABVD regimen).
• Case 4 — Autoimmune (Adult-Onset Still’s Disease): A 28-year-old woman has daily spiking fevers, arthralgia, and a salmon-pink rash. Labs: neutrophilia, high ferritin, negative ANA/RF. Diagnosis: Adult-onset Still’s disease. Management: NSAIDs or corticosteroids; consider biologics if refractory.
• Case 5 — Autoimmune (Giant Cell Arteritis): A 70-year-old woman presents with fever, weight loss, new headache, and scalp tenderness. ESR 110 mm/hr. Temporal artery tender and thickened. Diagnosis: Temporal arteritis presenting as PUO. Management: High-dose corticosteroids immediately; confirm with temporal artery biopsy.
• Case 6 — Miscellaneous (Drug Fever): A 65-year-old man on long-term antibiotics for osteomyelitis develops persistent fever without focus. All cultures negative. Fevers stop 48 hours after stopping beta-lactam therapy. Diagnosis: Drug-induced PUO. Management: Stop culprit drug; supportive care.

Teaching Commentary 🌡️

PUO is defined as fever >38.3 °C on several occasions, lasting >3 weeks, with no diagnosis after 1 week of inpatient investigation. Causes fall into 4 groups: 1. Infections (TB, endocarditis, abscesses). 2. Malignancies (lymphoma, leukaemia, renal carcinoma). 3. Autoimmune/Inflammatory (GCA, Still’s disease, vasculitis, SLE). 4. Miscellaneous (drug fever, thyroiditis, sarcoidosis). Approach: repeat history/exam, serial blood cultures, imaging (CXR, CT, PET-CT), autoimmune panel, consider biopsy. Always review medications. Management is cause-specific — avoid empirical steroids/antibiotics until diagnosis unless patient is acutely unstable.