1. Meera Ladwa

2.  Persistent temperatures of > 38.3 ⁰ C  Of more than 3 weeks duration  Of unknown cause despite 1 week of inpatient investigations

3.  Infections (30-40%) - Bacterial (TB, abscesses, endocarditis, osteomyelitis (discitis), Brucella, Histoplasma, Rickettsia) -Viral (HIV, CMV, EBV) -Parasites (malaria, toxoplasma, leishmaniasis, trypanosomiasis) -Spirochaetes (Borrelia, syphilis) -Fungal (candida in the immunosuppressed)

4.  Malignancies (20-30%) - Lymphomas -Leukaemias -Solid organ tumours (renal cell carcinoma, liver mets)

5.  Miscellaneous (20-30%) -Collagen vascular diseases (SLE, rheumatic fever, PAN, polymyalgia rheumatica, giant cell arteritis, Wegener’s granulomatosis) -Chronic inflammatory diseases - Crohns, sarcoid, rheumatoid arthritis -Drugs (penicillins, procainamide, isoniazid) -Endocrine (hyperthyroidism, Addison’s) -Inherited (Familial Mediterranean Fever) -Occult haematoma, occult thrombosis

6. -detailed travel and immunisation hx -detailed hx of previous surgery, dental work -occupational exposure or hobbies eg river water, animals, forests -contacts eg with TB -sexual history -drug history -IV drug use, blood transfusions, tattoos, piercings -family history

7.  Stigmata of infective endocarditis  Rashes  Lymphadenopathy  Joint swellings  Night sweats  Spinal tenderness  Hepato-splenomegaly

8.  Blood cultures – at least 3 from separate sites at separate times  Culture everything else – urine, sputum, stool. Culture of lymph node aspirate, bone marrow.  Sputum for AFB, tuberculin skin test, IGRA  Viral serology  CT abdomen  MR to look for osteomyelitis/discitis  Echo – consider TOE  Vasculitis screen – ANA, ESR, RhF, C3/C4  White cell scan, PET scan (occult abscess and tumours)

9.  PUO can be a diagnostic challenge!  Symptoms and signs can be subtle in the elderly and immunosuppressed  Common causes are infections, malignancies, and collagen vascular diseases  Remember to go back to the beginning; history and examination will inform appropriate investigations