FEVER OF UNKNOWN ORIGIN
fever of unknown originFUOpersistent feverprolonged feverunexplained feverclassic FUOnosocomial FUOneutropenic FUOHIV-related FUOPUOpyrexia of unknown origininfectious causes of FUOtuberculosisTB fevermiliary tuberculosisoccult infectionendocarditisdeep-seated abscessliver abscessrenal abscesssplenic abscesschronic infectionstyphoid feverbrucellosisCMV infectionEBV infectionHIV feverfungal feverhistoplasmosisrickettsial feverinflammatory diseases FUOadult-onset Still diseaseAOSDvasculitis fevergiant cell arteritistemporal arteritissarcoidosisSLE feverrheumatoid arthritis fevermalignancy feverlymphoma feverleukemia feverrenal cell carcinoma feverhepatocellular carcinoma fevercancer feverdrug feverthyrotoxicosis feverhyperthyroidism feverfamilial Mediterranean feverFMFfactitious feverfever workupFUO investigationsESR highCRP highPET-CT feverCT abdomen feverdiagnostic algorithm FUOFUO managementempirical antibioticsantipyretic therapyparacetamolceftriaxonevancomycinATTsteroids feverFUO differential diagnosisFUO clinical featuresFUO case-based learningFUO exam notesFUO guidelinesFUO study materialinternal medicine FUONEET PG general medicinepostgraduate medicine notes
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---
# 🔵 **FEVER OF UNKNOWN ORIGIN (PUO / FUO)**
### *A complete structured, stylish extraction from your images*
---
## 🌙 **Diurnal Variation in Body Temperature**
* **Maximum** temperature: *Evening*
* **Minimum** temperature: *Early morning (4 AM)*
* Normal diurnal variation: **<0.9°F**
**Reason for evening rise**
* ↑ BMR
* ↑ Muscular activity
---
## 🌡️ **Fever / Temperature Patterns**
* **AM** > 98.9°F
* **PM** > 99.9°F (due to circadian rhythm)
### Hyperpyrexia (>107°F)
* Associated with **heat stroke**
### Hypothermia (<35°C / 95°F)
* **Mild:** 32–35°C
* **Moderate:** 28–32°C
* **Severe:** <28°C
* ECG hallmark: **J-wave / Osborn wave**
### Measuring Core Temperature
* **Ideal site:** Pulmonary artery
* Lower esophagus > Rectal wall
* Rectal temp is **0.7°F higher** than oral
* Rectal temp is **more accurate**
---
# 🟢 **Patterns of Fever**
### 1. **Sustained / Continuous Fever**
* Never touches baseline
* Diurnal fluctuation <1°C
### 2. **Remittent Fever**
* Never touches baseline
* Fluctuation >1°C
### 3. **Intermittent Fever**
* Fever touches baseline
* Seen in **malaria**
### 4. **Relapsing Fever**
* Recurs every **3 days**
* e.g., *Borrelia recurrentis*, Rat-bite fever
---
# 🟣 **Fever Timelines & Malaria Patterns**
### Quotidian fever
Occurs **once daily**, touches baseline
### Double Quotidian Fever
Fever spikes **twice daily**
Seen in:
* Adult-onset Still’s disease
* Juvenile rheumatoid arthritis
### **Malaria patterns**
* **Tertian** (every 48 hrs): *P. vivax*, *P. ovale*
* **Quartan** (every 72 hrs): *P. malariae*
---
# 🟠 **Special Fever Behaviours**
### 📉 **Resolution by Crisis**
Fever suddenly falls
Seen in:
* Acute tonsillitis
* Pneumonia resolution
* Schistosomiasis
* Q fever
* Psittacosis
### 📉 **Resolution with Lysis**
Gradual decline in fever (step-ladder)
Occurs **after antibiotics**
### 📈 **Step-Ladder Fever (Typhoid)**
* Ciprofloxacin → lysis 5–6 days
* Ceftriaxone → faster resolution
---
# 🔴 **Causes of Fever of Unknown Origin**
## 1. **Infections > Inflammation**
* Atypical infection presentations
* Tuberculosis
* Osteomyelitis
* SAPHO syndrome
* Schnitzler syndrome
* PAPA syndrome
---
# 🔷 **Important Diagnostic Algorithm for PUO**
1. Fever >38.3°C for >3 weeks
2. Basic history + exam
3. Stop unnecessary antibiotics & steroids
4. Mandatory tests:
* ESR, CRP
* CBC
* LFT, RFT
* LDH
* ANA, RF
* CK
* Blood cultures ×3 (sterile)
* Urine culture
* CXR
* Abdominal USG
* Tuberculin test
5. Exclude **thermometer manipulation**
6. Stop suspected drug-related fever
---
## 🔍 **Potential Diagnostic Clues (PDC)**
### A. Fever + Headache
→ Do **Lumbar puncture / CSF**
* TB meningitis
* Cryptococcal meningitis
* Mollaret meningitis
### B. Fever + Cytopenia / Hepatosplenomegaly
→ **Bone marrow biopsy / aspiration**
### C. Fever + TB Features
→ **Liver biopsy** (CBNAAT preferred)
---
# 🟡 **Non-Infectious Inflammatory Disorders (NIID)**
1. **Large-vessel vasculitis**
* India: **Takayasu arteritis**
* Central Asia: **Behçet disease**
2. **Sarcoidosis**
* Breathlessness in young females
* Hilar lymphadenopathy
3. **Adult-onset Still disease**
4. **Polymyalgia Rheumatica**
5. **Tumors**
* Malignant lymphoma (common)
* Leukemia
6. **Drugs causing FUO**
* Allopurinol
* Lamotrigine, phenytoin
* Sulfa drugs
* Furosemide
* Quinidine
---
# 🔶 **HACEK Organisms**
* **H**: Haemophilus aphrophilus
* **A**: Aggregatibacter
* **C**: Cardiobacterium hominis
* **E**: Eikenella
* **K**: Kingella
Cause of **culture-negative endocarditis**
---
# 🟥 **Faget’s Sign / Relative Bradycardia**
Seen in:
* Gram-negative infections
* Tick-borne infections
### Mnemonic: **TBM CLR**
* **T**: Typhoid, Tularemia, Typhus
* **B**: Brucellosis, Babesia
* **M**: Mycoplasma
* **C**: Q fever, Corynebacterium
* **L**: Legionella
* **R**: Rickettsia
---
# 🟪 **Travel-related FUO Causes**
* Malaria
* Kala-azar
* Histoplasmosis (bat droppings)
* Coccidioidomycosis
---
# 🟤 **Case Summary from PET-CT (Your Screenshot)**
A 72-year-old female with chronic low-grade fever & fatigue
* CRP ↑
* Normocytic normochromic anemia
* PET-CT: **Uptake in subclavian artery → Large vessel vasculitis → Takayasu arteritis**
### Management
1. **Anti-TB therapy** *(if CNS signs)*
2. **NSAIDs** (Still disease)
3. **Colchicine** (FMF)
4. **Anakinra** (IL-1 blocker)
5. **Treat underlying cause**
---
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---
# ✅ **35 PUO Case Scenarios With Detailed Workup & Complete Management**
---
## **CASE 1 — GRANULOMATOUS HEPATITIS (SARCOIDOSIS)**
A 32-year-old woman with intermittent fever × 6 weeks, dry cough, weight loss, erythema nodosum. CXR shows bilateral hilar lymphadenopathy. ACE levels elevated. LFT mildly raised.
### **Diagnosis**
Sarcoidosis presenting as FUO.
### **Management**
* Prednisolone 0.5–1 mg/kg/day
* If refractory → Methotrexate
* Eye exam, ECG to rule systemic involvement
---
## **CASE 2 — SUBACUTE INFECTIVE ENDOCARDITIS (CULTURE-NEGATIVE)**
A 45-year-old male with low-grade fever × 8 weeks, clubbing, splinter hemorrhages. 3 × blood cultures sterile. Echo shows vegetation on mitral valve.
### **Diagnosis**
HACEK endocarditis.
### **Management**
* IV Ceftriaxone 2 g/day × 4 weeks
* If prosthetic valve → Add gentamicin
---
## **CASE 3 — TUBERCULAR LYMPHADENITIS**
A 27-year-old female, fever for 2 months, night sweats, painless cervical lymph node. FNAC → granulomatous inflammation, GeneXpert positive.
### **Management**
* ATT × 6 months (HRZE → HR)
---
## **CASE 4 — TEMPORAL ARTERITIS (GIANT CELL ARTERITIS)**
A 70-year-old woman with fever, headache, jaw claudication, ESR 110. PET-CT: uptake in temporal artery.
### **Management**
* Start Prednisolone 40–60 mg immediately
* Temporal artery biopsy within 1 week
---
## **CASE 5 — TAKAYASU ARTERITIS**
A 22-year-old female with FUO, absent left radial pulse, BP difference >10 mmHg. PET-CT shows aortic uptake.
### **Management**
* High-dose steroids
* Methotrexate or Mycophenolate
* Aspirin for vascular protection
---
## **CASE 6 — ADULT-ONSET STILL DISEASE**
Daily evening fever spike (>39°C), salmon-pink rash, polyarthritis, ferritin >5000.
### **Management**
* NSAIDs
* Steroids
* IL-1 inhibitors (Anakinra) if resistant
---
## **CASE 7 — LYMPHOMA (NHL)**
55-year-old man, FUO with profound night sweats, mediastinal nodes on CT, LDH ↑.
### **Management**
* Excisional lymph node biopsy
* R-CHOP regimen
---
## **CASE 8 — BRUCELLOSIS**
Shepherd from Rajasthan, fever 1 month, low back pain, hepatosplenomegaly. Brucella agglutination positive.
### **Management**
* Doxycycline + Rifampicin × 6 weeks
---
## **CASE 9 — Q FEVER (Coxiella burnetii)**
Cattle worker, FUO, hepatitis-like picture. IgM for C. burnetii positive.
### **Management**
* Doxycycline × 14 days
* Pregnant: Cotrimoxazole
---
## **CASE 10 — MALARIA (P. knowlesi – quotidian fever)**
Daily evening fever, splenomegaly. Rapid test negative. PCR positive for P. knowlesi.
### **Management**
* Artemisinin combination therapy
---
## **CASE 11 — DRUG FEVER (ALLOPURINOL)**
55-year-old on allopurinol for gout. FUO without any systemic signs, normal labs except mild eosinophilia.
### **Management**
* Stop allopurinol → fever resolves in 72 hrs
---
## **CASE 12 — FACTITIOUS FEVER (NURSING STUDENT)**
26-year-old female nurse, fluctuating fever only in hospital. Rectal temp normal at home. Inconsistent vitals.
### **Management**
* Psychiatric evaluation
* Remove access to thermometers
---
## **CASE 13 — LEPTOSPIROSIS**
Rice farmer, FUO, conjunctival suffusion, myalgia, bilirubin 4. MAT positive.
### **Management**
* Doxycycline OR IV ceftriaxone
---
## **CASE 14 — HEPATIC ABSCESS**
Alcoholic male with fever + RUQ pain. USG shows hypoechoic lesion.
### **Management**
* Metronidazole
* Drainage if >5 cm
---
## **CASE 15 — HIV SEROCONVERSION**
High-risk male, FUO, diffuse rash, oral ulcers. HIV Ag/Ab combo positive.
### **Management**
* Start ART immediately
---
## **CASE 16 — LIVER TB**
FUO with hepatomegaly. LFT: ALP high. Liver biopsy CBNAAT positive.
### **Management**
* ATT × 6 months
---
## **CASE 17 — DISSEMINATED HISTOPLASMOSIS**
Bat exposure, fever, oral ulcers, hepatosplenomegaly. Serum Histoplasma antigen positive.
### **Management**
* Amphotericin B → Itraconazole
---
## **CASE 18 — AUTOIMMUNE HEPATITIS**
Female with FUO, arthralgia, ALT↑, ANA positive, IgG ↑.
### **Management**
* Prednisolone + Azathioprine
---
## **CASE 19 — SUBACUTE THYROIDITIS**
Post-viral illness, fever, neck pain, suppressed TSH, elevated T4.
### **Management**
* NSAIDs
* Steroids if severe
---
## **CASE 20 — RELAPSING FEVER (BORRELIA)**
Traveller from Africa, cyclical fever every 7 days. Blood smear shows spirochetes.
### **Management**
* Doxycycline
---
## **CASE 21 — CHRONIC PYELONEPHRITIS**
Diabetic woman, fever, flank pain, sterile pyuria.
### **Management**
* Culture-guided antibiotics
* Control diabetes
---
## **CASE 22 — LIVER LYMPHOMA**
FUO, weight loss, liver lesions on PET, LDH high.
### **Management**
* Liver biopsy
* R-CHOP
---
## **CASE 23 — ENDOMETRITIS (POST-ABORTION)**
Fever for 2 weeks, foul discharge.
### **Management**
* Broad-spectrum IV antibiotics
* Remove retained products
---
## **CASE 24 — GIANT HEPATIC HEMANGIOMA (INFLAMMATORY)**
FUO with dull RUQ pain. CT shows 8 cm hemangioma.
### **Management**
* Usually observation
* Steroids if inflammatory variant
---
## **CASE 25 — MOLLARET MENINGITIS**
Recurrent fever with headache; CSF lymphocytic; HSV-2 PCR positive.
### **Management**
* Acyclovir
* Supportive care
---
## **CASE 26 — SPLENIC ABSCESS**
FUO, LUQ pain, infective endocarditis background.
### **Management**
* Drainage
* IV antibiotics
---
## **CASE 27 — RHEUMATOID ARTHRITIS–ASSOCIATED FUO**
Chronic joint pains, elevated ESR/CRP, rheumatoid factor high.
### **Management**
* DMARDs (Methotrexate)
* Steroids initially
---
## **CASE 28 — TB PERITONITIS**
Fever, abdominal distension, ascitic fluid SAAG <1.1, lymphocyte predominance.
### **Management**
* ATT × 6 months
---
## **CASE 29 — PROLONGED COVID INFECTION**
Immunocompromised patient with FUO, ongoing PCR positivity.
### **Management**
* Remdesivir ± monoclonals depending on variant
---
## **CASE 30 — LEUKEMIA (ALL)**
FUO + pallor + recurrent infections. CBC shows blasts.
### **Management**
* Bone marrow biopsy
* Induction chemotherapy
---
## **CASE 31 — CHOLEDOCHOLITHIASIS WITH CHOLANGITIS**
Fever + jaundice + RUQ pain. USG shows CBD stone.
### **Management**
* ERCP
* IV antibiotics
---
## **CASE 32 — TULAREMIA**
Exposure to rabbits; ulcer at finger + lymphadenopathy.
### **Management**
* Streptomycin OR Gentamicin
---
## **CASE 33 — BABESIOSIS**
Tick exposure, fever, anemia, hemoglobin drop. Maltese cross on smear.
### **Management**
* Atovaquone + Azithromycin
---
## **CASE 34 — OCCULT DENTAL ABSCESS**
FUO without localizing symptoms. CT face shows apical abscess.
### **Management**
* Drainage
* Amoxicillin-clavulanate
---
## **CASE 35 — FEVER OF UNKNOWN ORIGIN TRULY UNDIAGNOSED**
After complete PUO algorithm:
* No PDCs
* PET-CT normal
* All cultures negative
### **Management**
* NSAIDs for symptom control
* Close follow-up
* Re-evaluate every 2–4 weeks
---
# ✔️ Completed — 35 Excellent Real Case Scenarios
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Here are **15 fully detailed, high-yield, real-world PUO (Pyrexia of Unknown Origin) case scenarios** — each includes:
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---
# 🔵 **15 DETAILED CASE SCENARIOS IN PUO**
---
# **CASE 1 — Takayasu Arteritis (Large Vessel Vasculitis)**
**Patient:** 24-year-old female
**Symptoms:** Low-grade fever × 8 weeks, fatigue, dizziness on exertion, left arm BP not recordable.
**Exam:** Bruit over the left subclavian artery.
**Labs:** ESR 110, CRP ↑
**Imaging:** PET-CT shows circumferential uptake in aortic arch branches.
### **Diagnosis reasoning**
* Young female + pulse deficit + vascular uptake → Classic for Takayasu.
* Rule out: Endocarditis, TB, SLE.
### **Final Diagnosis:** *Takayasu Arteritis (Type I)*
### **Management**
* Prednisolone 1 mg/kg/day
* Methotrexate 15–20 mg weekly
* Aspirin 75 mg
* Biologics (Tocilizumab) if resistant
* Serial PET-CT monitoring
---
# **CASE 2 — Tubercular Lymphadenitis**
**Patient:** 29-year-old female
**Symptoms:** Fever with night sweats × 1 month, cervical LN swelling.
**Labs:** CBC normal; ESR ↑
**FNAC:** Granulomatous inflammation.
**CBNAAT:** MTB detected.
### **Final Diagnosis:** *Tubercular lymphadenitis causing PUO*
### **Management**
* ATT × 6 months (HRZE → HR)
* Monitor LFT
* Follow-up ultrasound
---
# **CASE 3 — Subacute Bacterial Endocarditis (Culture Negative, HACEK)**
**Patient:** 46-year-old male
**Symptoms:** Fever × 7 weeks, weight loss, joint pains.
**Signs:** Osler nodes, splinter hemorrhages.
**Blood cultures:** Sterile × 3
**Echo:** Vegetation on mitral valve.
### **Final Diagnosis:** *Culture-negative infective endocarditis (HACEK group)*
### **Management**
* IV Ceftriaxone 2 g/day × 4 weeks
* Add Gentamicin if severe
* Valve replacement if refractory
---
# **CASE 4 — Adult-Onset Still Disease (AOSD)**
**Patient:** 35-year-old woman
**Symptoms:** Daily fever spikes to 39–40°C, evanescent salmon rash, polyarthritis.
**Labs:** Ferritin 6500 ng/ml, ANA/RF negative.
### **Diagnosis:** *AOSD (Yamaguchi criteria)*
### **Management**
* NSAIDs initially
* Steroids 0.5–1 mg/kg
* Anakinra / Tocilizumab if steroid-resistant
---
# **CASE 5 — Sarcoidosis**
**Patient:** 33-year-old female
**Symptoms:** FUO × 2 months, dry cough, erythema nodosum.
**CXR:** Bilateral hilar lymphadenopathy.
**ACE level:** Elevated.
### **Diagnosis:** *Sarcoidosis with systemic involvement*
### **Management**
* Prednisolone 0.5 mg/kg/day
* Methotrexate if steroid-sparing
* Eye exam + ECG yearly
---
# **CASE 6 — Pyogenic Liver Abscess (Occult)**
**Patient:** 58-year-old diabetic male
**Symptoms:** FUO × 4 weeks, dull RUQ pain.
**USG:** 4 cm hypoechoic lesion.
### **Diagnosis:** *Silent liver abscess presenting as PUO*
### **Management**
* IV Ceftriaxone + Metronidazole
* Percutaneous drainage if >5 cm
* Control diabetes
---
# **CASE 7 — Disseminated Histoplasmosis**
**Patient:** 40-year-old cave tourist
**Symptoms:** FUO, oral ulcers, weight loss.
**Exam:** Hepatosplenomegaly.
**Labs:** Pancytopenia.
**Urine antigen:** Histoplasma positive.
### **Diagnosis:** *Disseminated fungal infection*
### **Management**
* Liposomal Amphotericin B × 2 weeks
* Itraconazole × 12 weeks
* Monitor renal function
---
# **CASE 8 — Q Fever (Coxiella burnetii)**
**Patient:** Dairy farm worker
**Symptoms:** Fever × 1 month, headache, mild hepatitis.
**Serology:** Phase II IgM positive.
### **Diagnosis:** *Q fever presenting as PUO*
### **Management**
* Doxycycline × 14 days
* Pregnant: Cotrimoxazole
---
# **CASE 9 — Lymphoma (NHL)**
**Patient:** 62-year-old male
**Symptoms:** FUO, drenching night sweats.
**Exam:** No lymph nodes palpable.
**PET-CT:** FDG-avid para-aortic nodes.
**LDH:** Elevated.
### **Diagnosis:** *Occult Non-Hodgkin Lymphoma*
### **Management**
* Lymph node biopsy
* R-CHOP chemotherapy
* PET-CT response evaluation
---
# **CASE 10 — Factitious Fever**
**Patient:** 26-year-old nursing student
**Symptoms:** Fever reported only in hospital.
**Observation:** Rectal temp normal when monitored; oral thermometer manipulated.
**Labs:** All normal.
### **Diagnosis:** *Factitious disorder causing PUO*
### **Management**
* Psychiatric evaluation
* Remove access to thermometer
* Supportive therapy
---
# **CASE 11 — Brucellosis**
**Patient:** Goat herder
**Symptoms:** FUO, backache, hepatosplenomegaly.
**Labs:** LFT mildly raised, blood culture negative.
**Serology:** SAT positive.
### **Diagnosis:** *Brucellosis*
### **Management**
* Doxycycline + Rifampicin × 6 weeks
* For spondylitis: Add streptomycin × 2 weeks
---
# **CASE 12 — Tuberculous Peritonitis**
**Patient:** 48-year-old female
**Symptoms:** Fever, abdominal distension, weight loss.
**Ascitic fluid:** SAAG <1.1, lymphocytic.
**Adenosine Deaminase:** High.
### **Diagnosis:** *TB peritonitis*
### **Management**
* ATT × 6–9 months
* Monitor for paradoxical worsening
---
# **CASE 13 — Relapsing Fever (Borrelia)**
**Patient:** Foreign traveler
**Symptoms:** Fever every 5–7 days, each lasting 48 hours.
**Smear:** Spirochetes visible during fever peaks.
### **Diagnosis:** *Tick-borne relapsing fever*
### **Management**
* Doxycycline
* Watch for Jarisch–Herxheimer reaction
---
# **CASE 14 — Subacute Thyroiditis (De Quervain)**
**Patient:** 30-year-old female post-viral infection
**Symptoms:** Fever × 4 weeks, neck pain radiating to jaw.
**Labs:** TSH ↓, T4 ↑, ESR ↑
**USG:** Hypoechoic painful thyroid.
### **Diagnosis:** *Subacute granulomatous thyroiditis*
### **Management**
* NSAIDs → If severe, Prednisolone
* Beta-blockers for hyperthyroid symptoms
---
# **CASE 15 — Hidden Dental Abscess**
**Patient:** 41-year-old man
**Symptoms:** FUO × 1 month, no localizing signs.
**CT Face:** Apical abscess over upper premolar.
### **Diagnosis:** *Occult dental abscess causing PUO*
### **Management**
* Drainage
* Amoxicillin–clavulanate × 7–10 days
* Dental extraction if needed
---
# ✔️ **15 DETAILED TRUSTED CASES COMPLETED**
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