A comprehensive history and a thorough physical examination can aid in the diagnosis of fever of unknown origin.

• History: Thorough history with a focus on the most likely aetiology based on the patient’s symptoms is the key to identifying the origin of FUO. Information about previous illnesses, home medications, localizing symptoms, alcohol intake, occupational exposures, pets, travel, and familial disorders should be taken. The diagnosis depends on complete and repeated history taking. Immunization history, Dental history, Nutrition and weight history, Surgery, trauma, or procedures history are also vital to note. Fever pattern analysis can provide additional clues to identify the causative agent.^[1]
• Physical examination: In cases of infectious FUO, important physical exam findings include heart murmur, suggestive of bacterial endocarditis, spinal tenderness indicating vertebral osteomyelitis, splenomegaly concerning for miliary TB, Epstein-Barr virus (EBV), and cytomegalovirus (CMV), and epididymal nodule indicating extrapulmonary TB. In cases of malignancies, physical examinations may include relative bradycardia indicative of lymphoma/ CNS malignancy, a new heart murmur denoting atrial myxoma, or sternal tenderness concerning a myeloproliferative disorder. Isolated hepatomegaly and FUO might be indicative of a hepatoma or liver metastases. In non-infectious FUO, fever distribution analysis can differentiate between periarteritis nodosa and adult Still disease. On physical examination, oral ulcers (Behcet disease, systemic lupus erythematosus [SLE]), unequal pulses (Takayasu arteritis), rashes (sarcoidosis, SLE, adult Still disease), and lymphadenopathy (SLE, RA, sarcoidosis) can be identified.  On physical examination, splenomegaly is an important diagnostic tool for identifying Crohn disease and liver cirrhosis.1
• Recommended diagnostic tools for investigating fever of unknown origin (FUO) are- 
• Non-invasive tests: 

1. complete blood count (CBC) with differential count
2. chest X-ray
3. complete metabolic panel 
4. urinalysis with microscopy
5. urine culture
6. erythrocyte sedimentation rate (ESR)
7. C-reactive protein (CRP) value
8. antinuclear antibodies (ANA)
9. rheumatoid factor (RA)
10. lactate dehydrogenase
11. cytomegalovirus IgM/PCR
12. heterophile antibody test
13. tuberculin skin test
14. HIV testing and
15. computed tomography (CT) scan of the abdomen and chest
16. echocardiography. 

• Nuclear Medicine Tests: Recent European studies suggest that fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan can aid in detecting anatomic localization of infectious, inflammatory, or neoplastic processes.
• Invasive Tests: The most common invasive tests for diagnosing FUO are biopsies of lymph nodes, liver, bone marrow, epididymal nodule, and temporal artery. Endoscopic examination of the upper and lower GI tract should be done, including retrograde cholangiography if indicated as for Crohn disease, biliary tract disease, and gastrointestinal tumours.1 Available data demonstrate that ultrasound-guided synovial biopsy is an effective, safe, and well-tolerated method for retrieving quality synovial tissue from any joint, with impacts on diagnosis and treatment.