1. 4MB Clinical Problem-Solving Dr. Gerard Flaherty Dept. of Medicine

2. 42-yr-old ♂ Presenting Complaint: Pyrexia of Unknown Origin

3. Definition “Illness of more than three weeks’ duration, fever higher than 38.3°C (101°F) on several occasions, and diagnosis uncertain after one week of study in hospital.” (Petersdorf and Beeson, 1961)

4. Definition “Fever that does not resolve spontaneously in the period expected for self-limited infection and whose cause cannot be ascertained despite considerable diagnostic effort.” (Arnow and Flaherty, 1997)

5. History ?Night sweats ?Weight loss ?Pruritus Symptoms of underlying illness Previous illnesses Medications Occupational exposures Pets Foreign travel Family history

6. Physical Examination Vital signs (?relative bradycardia) ?Jaundice Anaemia ?Hyperpigmentation Abdominal tenderness Hepatosplenomegaly Abdominal mass ENT examination Examine teeth ?Murmurs ?Wounds Auscultate chest Lymphadenopathy Clubbing Joint swelling Rash Thickened temporal artery Iritis Mouth ulcers Leg swelling (?DVT) Thyroid tenderness Signs of thyrotoxicosis Gouty tophi Tender prostate on PR exam Testicular tenderness

7. 76-yr-old ♂ with headache and scalp tenderness. Give the diagnosis.

8. Minimum diagnostic work-up to qualify as PUO Full history Repeated examination FBC SMAC, including LDH ESR Antinuclear antibodies Rheumatoid factor HIV serology MSU ACE Blood cultures ×3 CMV serology Monospot Mantoux test Chest radiograph Ultrasound Abdomen CT Abdomen

9. Further Investigations Discontinue as many medications as possible Tumour markers Echocardiogram Gallium-67 or indium-111-labelled white cell scan Excision biopsy Laparotomy Temporal artery biopsy Sputum for acid-fast bacilli Bone marrow biopsy

10. Infective endocarditis

11. Differential Diagnosis Disease categories 1. Infection 2. Neoplasia 3. Collagen vascular diseases

12. The causes of Pyrexia of Unknown Origin are usually familiar diseases with uncommon presentations rather than rare disorders.

13. Failure to utilise findings correctly, delay in requesting appropriate tests, and misinterpretation of results all contribute to missed diagnoses.

14. Infection (a partial list!) Intraabdominal abscess; Appendicitis; Cholecystitis; Cholangitis; Mesenteric lymphadenitis; Tubo-ovarian abscess; Intracranial abscess; Sinusitis; Mastoiditis; Otitis media; Dental abscess; Chronic pharyngitis; Tracheobronchitis; Lung abscess; Septic jugular phlebitis; Mycotic aneurysm; Endocarditis; IV catheter infection; Vascular graft infection; Wound infection; Osteomyelitis; Infected joint prosthesis; Pyelonephritis; Prostatitis; TB; Lyme disease; Relapsing fever; Syphilis; Q fever; Legionella; Salmonella; Listeria; Campylobacter; Brucellosis; Psittacosis; Chlamydia pneumoniae; Gonorrhoea; Meningococcaemia; Actinomycosis; Whipple’s disease; Candidaemia; Cryptococcus; Histoplasma; Coccidioidomycosis; Blastomycosis; Aspergillosis; Pneumocystis carinii; Visceral leishmaniasis; Malaria; Babesiosis; Toxoplasmosis; Schistosomiasis; Toxocariasis; Amoebiasis; Hydatid cyst; Trypanosomiasis; CMV; HIV, Herpes simplex; Epstein-Barr virus.

15. Hepatic abscess

16. Neoplasia Pyrexia of unknown origin has been reported in association with 46 different malignancies. e.g. Lymphoma Renal-cell carcinoma

17. Collagen vascular diseases Adult Still’s disease; SLE; Cryoglobulinaemia; Reiter’s syndrome; Rheumatic fever; Giant cell arteritis / Polymyalgia rheumatica; Wegener’s granulomatosis; Ankylosing spondylitis; Behçet’s disease; Polyarteritis nodosa; Sjögren’s syndrome; Polymyositis; Rheumatoid arthritis; Erythema multiforme; Erythema nodosum; Relapsing polychondritis; Mixed connective-tissue disease; Takayasu’s arteritis; Felty’s syndrome; Eosinophilic fasciitis.

18. Rheumatoid arthritis

19. 30-yr-old ♀ with arthralgia and pleuritic chest pain. Give the diagnosis.

20. Miscellaneous Haematoma; Thrombosis; Aortic dissection; Femoral aneurysm; Dressler’s syndrome; Atrial myxoma; Drug fever; Familial Mediterranean fever; Familial Hibernian fever; Inflammatory bowel disease; Sarcoidosis; Subacute thyroiditis; Hyperthyroidism; Addison’s disease; Hypothalamic hypopituitarism; Gout; Pseudogout; Cirrhosis; Chronic active hepatitis; Alcoholic hepatitis; Kawasaki’s disease; Gaucher’s disease; Fabry’s disease; Cholesterol emboli; Sickle cell disease; Cyclic neutropenia; Hamman-Rich syndrome; Hypersensitivity pneumonitis; Extrinsic allergic alveolitis; Stroke; Brain tumour; Encephalitis; Psychogenic fever; Factitious fever.

21. 24-yr-old ♂ with dyspnoea and a painful red eye. Give the diagnosis.

22. 38-yr-old ♀ with bloody diarrhoea and arthralgia. Give the diagnosis.

23. Management of underlying conditions

24. References 1. Arnow PM, Flaherty JP (1997) Fever of unknown origin. Lancet 350: 57-80.

25. Next week…. Headache