case study about fever of unknown origin

Detailed information about fever of unknown origin

1. Case 1

2. 1. Patient Details and History
Name: Mr. Faheem Rahman
Age: 37 years
Gender: Male
Occupation: High school teacher
Marital status: Married
Address: Almaty, Kazakhstan
Date of admission: 09 October 2025 Chief Complaint

Persistent fever for 4 weeks (temperature up to 39.5°C)

Associated fatigue, loss of appetite, and weight loss (~5 kg in one month)

3. History of Present Illness
Mr. Faheem reports a continuous fever for the last four weeks, fluctuating between 38°C and 39.5°C, with no chills or rigors. The fever was initially low-grade but has gradually increased in intensity.
He also notes:
General malaise and body ache
Loss of appetite and unintentional weight loss
Mild headache (dull, not localized)
No cough, sore throat, or urinary symptoms
No rash, joint pain, or recent travel No known sick contacts He visited several local clinics and was prescribed empirical antibiotics (amoxicillin- clavulanate , azithromycin) for presumed infection, but fever persisted despite treatment.

4. Past Medical History
No known chronic illnesses (no diabetes, hypertension, or tuberculosis).
No history of recent hospitalization or surgery.
No immunosuppressive drug use.
Vaccinations up to date. Family and Social History
Non-smoker, occasional tea drinker, no alcohol.
Family history: father had pulmonary tuberculosis 10 years ago (treated).
No pets at home, no animal exposure.
No travel outside the city recently.

5. | System | Findings |
| ---------------- | ------------------------------------- |
| Respiratory | No cough, hemoptysis , or dyspnea |
| Cardiovascular | No chest pain or palpitations |
| Gastrointestinal | No diarrhea or abdominal pain |
| Genitourinary | No burning micturition or discharge |
| Neurological | Occasional mild headache, no seizures |
| Musculoskeletal | Mild myalgia, no joint swelling |

6. | Parameter | Findings |
| ------------------ | ---------------------------------------------------------------- |
| Temperature | 39.2°C |
| Pulse | 102 bpm (regular) |
| Blood pressure | 118/78 mmHg |
| Respiratory rate | 18/min |
| Oxygen saturation | 98% on room air |
| General appearance | Pale, tired, no jaundice or cyanosis |
| Skin | No rash, petechiae , or lesions |
| Lymph nodes | Slightly enlarged, non-tender left cervical lymph node (~1.5 cm) |
| Cardiovascular | Normal S1, S2, no murmur |
| Respiratory | Clear breath sounds |
| Abdomen | Mild splenomegaly (+2 cm below costal margin), no hepatomegaly |
| Neurological | No focal deficits |

7. Investigations and Results

Since fever persisted beyond 3 weeks with no clear cause, a structured FUO workup was initiated. | Test | Result | Normal Range | Interpretation |
| -------------------- | -------------------------------------------------- | ------------ | ---------------------- |
| CBC | Hb 10.8 g/dL, WBC 8,500/mm³, Platelets 240,000/mm³ | Hb : 12–16 | Mild anemia |
| ESR | 75 mm/hr | <20 | Markedly elevated |
| CRP | 68 mg/L | <5 | Significantly elevated |
| Liver Function Tests | Normal bilirubin, ALT 32, AST 30 | — | Normal |
| Renal Function | Urea 30 mg/dL, Creatinine 0.9 mg/dL | — | Normal |
| Blood glucose | 94 mg/dL | — | Normal |

8. URINE AND STOOL TEST | Test | Result | Interpretation |
| ------------- | ---------------------------- | -------------- |
| Urine routine | Normal, no WBC/RBC | No UTI |
| Urine culture | Sterile | — |
| Stool exam | No ova/cyst, no occult blood | Normal |

9. Microbiological and serological test | Test | Result | Interpretation |
| --------------------------- | --------------------- | -------------- |
| Blood cultures (×3) | Negative after 5 days | No bacteremia |
| Widal test | Negative | No typhoid |
| Mantoux (PPD) | 15 mm induration | Positive |
| HIV ELISA | Negative | — |
| Hepatitis B surface antigen | Negative | — |
| Hepatitis C antibody | Negative | — |
| ANA, Rheumatoid factor | Negative | — |

10. Imaging Studies

Chest X-ray: Normal, no infiltrates or lesions.
Abdominal ultrasound: Mild splenomegaly, normal liver, no abscess or mass.
CT scan (Chest & Abdomen):
Small multiple enlarged para-aortic and mesenteric lymph nodes (1–2 cm)
No abscess or malignancy signs
Spleen mildly enlarged
Echocardiography: No vegetations , ruling out infective endocarditis.

11. Advanced diagnostic test | Test | Result | Interpretation |
| ------------------------------------- | --------------------------------------- | ------------------------------- |
| Bone marrow aspiration | Granulomatous inflammation | Suggestive of TB or sarcoidosis |
| AFB stain and culture | Positive for Mycobacterium tuberculosis | Confirmed cause |
| Interferon-gamma release assay (IGRA) | Positive | Supports TB infection |

12. Preliminary diagnosis Based on the presence of fever >3 weeks, elevated ESR, lymphadenopathy, splenomegaly, and granulomatous inflammation in bone marrow, the differential diagnoses considered were:
Tuberculosis (disseminated or extrapulmonary )
Lymphoma
Connective tissue disease (SLE, vasculitis) Subacute bacterial infection (endocarditis)

13. Final diagnosis 🔹 Fever of Unknown Origin due to Disseminated ( Extrapulmonary ) Tuberculosis
Supporting evidence:
Fever >3 weeks not responding to antibiotics
Positive Mantoux and IGRA tests
Granulomatous inflammation in bone marrow
AFB-positive culture confirming Mycobacterium tuberculosis
Absence of other causes on imaging and lab results

14. Treatment plan A. Anti-tubercular Therapy (ATT)
According to WHO standard regimen for adult TB (Category I): | Phase | Duration | Drugs | Dosage |
| -------------------------------- | ---------------- | ---------------------------- | ------ |
| Intensive Phase | 2 months | **Isoniazid (H)** 300 mg/day | |
| **Rifampicin (R)** 600 mg/day | | | |
| **Pyrazinamide (Z)** 1500 mg/day | | | |
| ** Ethambutol (E)** 1200 mg/day | Once daily, oral | | |
| Continuation Phase | 4 months | **Isoniazid (H)** 300 mg/day | |
| **Rifampicin (R)** 600 mg/day | Once daily, oral | | |

15. Supportive Treatment | Medication | Dose | Purpose |
| ------------------------------- | -------------- | ------------------------------------ |
| Paracetamol | 500 mg q6h PRN | Fever relief |
| Pyridoxine | 25 mg/day | Prevent INH-induced neuropathy |
| Iron & multivitamin supplements | Daily | Correct anemia and improve nutrition |
| High-protein diet | — | Nutritional support |

16. Monitoring and Follow-Up Baseline LFTs before starting ATT and repeated every month.
Monthly clinical evaluation of fever and symptoms.
Repeat CBC and ESR after 2 months to assess response.
Adherence counseling for completion of therapy.

17. Fever of Unknown Origin (FUO) is defined as:
Fever ≥38.3°C (101°F) lasting for ≥3 weeks with no diagnosis after 1 week of inpatient investigation.
Categories of FUO:
Classical FUO: in immunocompetent individuals
Nosocomial FUO: in hospitalized patients Neutropenic FUO: in neutropenic /immunocompromised
HIV-associated FUO

18. Most common causes of FUO:
Infections (30–40%) — e.g., tuberculosis, abscess, endocarditis
Neoplasms (20–30%) — e.g., lymphoma, leukemia Collagen vascular diseases (10–20%) — e.g., SLE, vasculitis
Miscellaneous (15%) — drug fever, thyroiditis
Undiagnosed (up to 10%)