The Physicians Fever

1. The Physicians Fever MIDG 14/4/2009 Alistair Reid St Vincent�s Hospital

2. Case 69yo man Phx IHD, angioplasty with stents Bilateral Knee replacements HT T2DM, on insulin Hypercholesterolaemia Meds Insulin Metformin Frusemide Clopidogrel Irbesartan

3. HOPC Felt �hot� Sat morning ? fever Collapse Fall from chair while working on computer at desk on Sat evening � wife discovered him Presumed syncope Confused Observed overnight in ED

4. Progress in ED Still confused following morning CT Brain � old lacunar infarcts Temp to 38 noted Overnight cardiac monitoring NAD Med Reg review

5. Med reg Review No headache/photophobia/neck stiffness No cough/SOB No chest pain or palpitations No diarrhea/vomiting/ abdo pain/ dysuria Urinary incontinence - one episode in ED No history of similar events Obese Not orientated to person or place Temp 38.2 HR 95, BP 150/75, O2Sats 98% Ataxia otherwise neuro unremarkable Chest clear, abdo lax non tender No rash

6. Investigations HB 120 WCC 6.1 plts 220 LFTs NAD U&E NAD CRP 153 CXR NAD FWT NAD BC taken LP attempted � difficult - abandoned CT Brain � old lacunar infarct

7. Differential Diagnosis What thoughts would an ID clinician have? CNS infection Bacterial, Cryptococcal, HSV encephalitis, brain abscess Sepsis of any focus with delerium Urine, prostate, respiratory, sinuses, intra-abdominal Stroke ? brainstem Cardiovascular eg: ischeamia with secondary cause of fever

8. Initial Treatment by Med Unit ? Encephalitis ? CVA Admitted under gen med IV Aciclovir started 10mg/kg q8h Antibacterial cover not added

9. Investigations LP under fluoroscopy Leucocytes <1 Erythrocytes <1 Protein(g/l): 0.31 Glucose(mmol/l): 6.8 HSV PCR negative AFB not seen

10. ID review 3 days after admission day 4 of illness Temp 39 C but haemodynamically stable Confused Not orientated to person, place or time Could follow commands Speaking fluently

11. ID review cont Born Poland, migrated as young man Married, 2 children, Ex grocer No hobbies No ETOH excess No recent travel � overseas or country areas No exposure to animals/birds ?confusion 6 months

12. ID review cont ARF, serum creatinine 300 ?Aciclovir-> ceased Urinary unremarkable Blood Cultures unremarkable Added tests to CSF Indian Ink: Cryptococcus not detected Cryptococcal antigen not detected (CSF and Serum) AFB negative Started broad spectrum antibiotic cover IV Ceftriaxone, Vancomycin, Metronidazole

13. Further investigation Infective Rule out CNS infection (abscess) � view brainstem Other focus � liver/ diverticular abscess Tuberculosis Other Non infective Vasculitis Drug fever Malignancy Other

14. Further investigations MRI/MRA Brain mild atrophy Otherwise NAD CT chest/abdo/pelvis NAD No CT angio due to renal failure Syphilis serology negative HIV negative Throat - Resp multiplex PCR neg

15. Further investigaton Vasculitic screen negative Legionella urinary antigen - negative CMV Igm negative, IgG positive EBV IgM negative, IgG positive Atypical pneumonia serology � negative Quantiferon negative

16. Progress day 6 Still febrile to 39, still confused (worse at night) Respiratory deterioration overnight CXR � bilateral infiltrate ICU admission Changed to meropenem, vancomycin Added Azithromycin Did we miss legionella?

17. Progress in ICU Diuresis Rapid improvement Likely overfilled for ARF Renal function improving Psych review Delerium with underlying frontotemporal dementia

18. Progress day 7 In ICU ID team grand round ?drug fever - ? Clopidogrel � but 5 years of Rx ? evolving vasculitis ESR 63 tender right temporal artery noted �ropey� to palpation

19. The answer! Right temporal artery biopsy - Giant cell arteritis confirmed lymphohistiocytic inflammatory infiltrate within the adventitia extending into the tunica media Fever abated without treatment Steroids commenced

20. Undifferentiated fever Acute undifferentiated fever <72 hours most turn out to have a focus which becomes evident over 1-2days or via simple Ix Priority is picking severe sepsis early PUO >3 weeks fever despite Ix High likelihood non-infective cause What about in between?

21. 4-10 day fever �The Consultants Fever� a focus of acute infection has not become evident (despite clinical assessment plus simple Ix) So�it gets referred to a consultant Not yet a true�PUO� �A particular group of infections come to the fore�

22. Approach Thorough history Travel Occupation Animal exposure Medications Risk factors for STI�s Observe evolution of disease Think broadly Infectious Non-infectious Don�t miss severe bacterial infection

23. Infectious causes CMV, EBV, Toxo HIV seroconversion Hep A prodrome Influenza Atypical pneumonia Secondary Syphilis Abscess Liver, pericolic, psoas muscle Zoonoses: Q fever, Brucella, leptospirosis, psittacosis, bartonella Tuberculosis Typhoid Infective endocarditis Malaria Lyme disease

24. Non-infectious causes Drug fever: eg betalactams Thromboembolic disease Vasculitis Granulomatous disorders Sarcoid, granulomatous hepatitis Inflammatory: Pericarditis, Crohn�s disease Autoimmune: Thyroiditis, haemolytic anaemia Malignancy: Lymphoma, Renal cell Ca, adenoCa Metabolic: Gout, Addisons, hyperthyroidism Vascular: post AMI, CVA, aortic dissection Crush injuries Factitious

25. Investigations Blood cultures x 3 Tuberculin skin test/quantiferon gold HIV antibody assay Heterophile antibody, EBV serology CMV serology Vasculitic screen ESR, ANA, ANCA, sPEP, LDH TFTs CT scan of abdomen / chest Angiography Liver biopsy Temp artery Bx BMAT

26. Temporal arteritis May present with collapse and/or confusion Fever >39 degrees celsius in 15% of patients ESR sensitive (96%) but not specific

27. Questions?

28. Legionnaires Patients are commonly lethargic with headache and occasionally stupor Up to 53% have neurological manifestations Classical presentation � �atypical becoming typical pneumonia� Early non respiratory symptoms predominate and then respiratory symptoms develop with time � can deteriorate rapidly