PYREXIA OF

UNKNOWN ORIGIN

PRESENTED BY:TANVI SINGLA

Regulates normal body temperature

Normal Rectal temp. being 97.7-99.5°F

Oral temp. being 0.7°F lower than rectal

while axillary being 1.2°F lower than rectal.

Daily normal variation being 0.5-1°FWith evening temperatures being higher than the morning

If body temp. exceeds normal variation in an individual, that’s called FEVER

Liebermiester’s Rule: With each degree centigrade rise in body temp. , heart rate increase by 8 per minExcept in those diseases where relative bradycardia sets in.

DEFINITION

PETERSDORF AND BEESON

1961

TEMP> 101°F ON SEVERAL OCCASIONS

DURATION OF FEVER > 3

WEEKS

FAILURE TO REACH DIAGNOSIS DESPITE

1 WEEK OF INPATIENT INV.

DURACK & STREET’S CLASSIFICATION

CLASSIC

PUO

•3 OUTPATIENT VISITS OR 3 DAYS IN HOSPITAL W/O ELUCIDATION OF CAUSE

•OR 1 WEEK OF “INTELLIGENT AND INVASIVE” AMBULATORY INV.

NOSOCOMI

AL PUO

•IN HOSPITALISED PATIENTS TEMP> 101°F DEVELOPS ON SEVERAL OCCASIONS WHO IS RECEIVING ACUTE CARE AND WHOM WAS NOT MANIFEST OR INCUBATING AT TIME OF ADMISSION

•3 DAYS OF INV. INCLUDING ATLEAST 2 DAYS INCUBATION OF CULTURES

NEUTROPENICPUO

•TEMP> 101°F ON SEVERAL OCCASIONS IN PATIENTS WHOSE NEUTROPHIL COUNT IS <500uL(n 2-7x10^3) OR EXPECTED TO FALL WITHIN 1-2 DAYS

•NO SPECIFIC CAUSE IDENTIFIED 3 DAYS OF INV. INCLUDING ATLEAST 2 DAYS INCUBATION OF CULTURES

HIV- ASSOCIATE

D PUO • >101°F ON SEVERAL OCCASIONS OVER A PERIOD OF >4 WEEKS FOR

OUTPT. OR >3 DAYS FOR INPT. WITH HIV•NO SOURCE REVELAED OVER 3 DAYS INV. INCLUDING 2 DAYS INCUBATION OF CULTURES

COMMON CAUSES OF PUO

TB being the no. 1

DRUG FEVER

INFECTIONSBacterial Infection: Common etiologies

• Chronic sinusitis• Mastoiditis• Salmonellosis • Abscesses(subdiaphragmatic,liver,renal,retroperitoneal,

paraspinal)• Chronic prostatitis• Pyelonephritis• Bacterial endocarditis(esp if caused by HACEK group)• Osteomyelitis(esp in cases of implantation of prostheses)

Uncommon•Leptospirosis•Brucellosis•Chlamydia•Rickettsial infections(Q fever, Scrub Typhus, Rocky Mountain Spotted fever)

•TB meningitis•Spinal TB•Bone and joint TB•Grannulomatous hepatitis•Abdominal TB•Genitourinary TB•Tubercular lymphadenopathy

VIRAL: • CMV•EBV•HIV

FUNGAL:•Blastomycosis•Histoplasmosis•Cryptococcus

PARASITIC•Malaria•Toxoplasmosis•Leishmaniasis

As the duration of fever increases, it is less likely that it’ll be of infectious

origin.

NEOPLASMS

All kinds of

AUTO-IMMUNE DISORDERS

•SLE•Vasculitis•Adult still’s disease•Temporal arteritis

MISCELLANEOUS

HyperthyroidismPhaechromocytomaMetabolic disorders DRUG FEVER: •Antimicrobials(Beta lactum antibiotics)•Cardiovascular (Quinidine)•Antineoplastic•Antiepileptic (phenytoin)

A 45 year old man was admitted to the ICU with acute MI, thrombolysed and

reperfused, but then went into persistent hypotension following a cardiac arrest. He developed fever on Day 5. Routine blood

investigation showed a polymorpho-nuclear leucocytosis. Blood culture was

diagnostic.What could it be???

NOSOCOMIAL PUOETIOLOGY

InfectionsNon infectious causeUndiagnosedOthers

•Accounts for 50%• suspects will be I/V lines, prothesis, septic phlebitis•Focused approach on sites where occult infection may be present eg sinuses of intubated patients.

Accounts for 25%•Acalculous cholecystitis•DVT•Pulmonary Embolism

Includes drug fever, withdrawal or transfusion rxns or post myocardial infarction syndrome.

20% remains undiagnosed

A 14 year old boy was admitted with high grade fever and pallor. On examination no hepatosplenomegaly, lymphadenopathy or bone tenderness were present. The blood counts were as follows: Hb 8gm%, TLC 3800, P8 L86 E4 M2, ESR 20 mm in 1st hr. Platelet count 2.5 lakhs.

What could it be???

NEUTROPENIC INFECTIONSPatients on chemotherapy or immune deficiencies are more susceptible to:•Oppurtunistic bacterial infections•Fungal infections like candidiasis•Bacteremic infections•Infections involving catheters•Perianal infections

Most common etiological agents are:•Aspergillus•Candida•CMV•Herpes simplex

HIV – associated PUOHIV Infection as such may be the causeOther secondary causes are:Pulmonary TuberculosisPneumocystis InfectionToxoplasmosisSalmonellosisCryptococciosisCytomegalovirus infectionM. Avium or M. IntracellulareNon-Hodgkin’s LymphomaDrug induced fever

PYREXIA OF

UNKNOWN ORIGIN

- A CLINICAL APPROACH

HISTORY TAKINGHistory of present illness1)Onset : • Acute: Malaria, pyogenic infection• Gradual: TB, typhoid fever

2) Character: high grade- UTI, TB, malaria, drug

3) Pattern: Whether returns to normal or not• Sustained/ persistent: typhoid, drugs

•Intermittent fever: Daily spikes: Abscesses, TB, SchistosomiasisTwice – daily spikes: Leishmaniasis•Relapsing/recurrent fever: Non falciparum malaria, Brucellosis, Hodgkin’s

4) Antecedents -Prior to onset of fever:•Dental extraction: infective endocarditis•Urinary catheterization: UTI, bacteremia

5) Associated symptoms:• Rigors and chills Bacterial, rickettsial and protozoal diseaseInfluenza, lyphoma, leukaemia, drug-induced•Night sweats: TB, Hodgkin’s lymphoma•Loss of weight: malignancy, TB•Cough and dyspnoea: miliary TB, multiple pulm. Emboli, CMV•Headache: Giant cell arteritis•Joint pain: RA,SLE, vasculitis

• Abd. Pain– Cholangitis, biliary obstruction, perinephric abscess,

Crohn’s disease, dissecting aneuryms, gynaecological infection

• Bone pain– Osteomyelitis, lymphoma

• Sorethroat– IM, retropharyngeal abscess, post-Streptococcal

infection• Dysuria, rectal pain

– Prostatic abscess, UTI• Altered bowel habit

– IBD, typhoid fever, schistosomiasis, amoebiasis• Skin rash

– Gonococcal infection, PAN， NHL, dengue fever

• Past Medical History– Malignancy = leukemia, lymphoma, hepatocellular ca– HIV infection– DM– IBD– collagen vascular disease-SLE, RA, giant cell arteritis – TB– Heart disease: valvular heart disease

• Past Surgical History– Post splenectomy/ post- transplantation– Prosthetic heart valve– Catheter, AV fistula – Recent surgery/ operation

• Drug History– Drug fever occur within 3 months after start

of drugs• may cause low grade fever, usually

associated with rash• Due to the allergic reaction, direct effect of

drug which impair temperature regulation (e.g. phenothiazine)

• E.g. Antiarrhythmic drug: procainamide, quinidine; Antimicrobial agent: penicillin, cephalosporin, hydralazine

– After fever: may modify clinical pictures, mask certain infection e.g. SBE, antibiotic allergy

Family History– Anyone in family has similar problem:

TB, familial Mediterranian fever

• Social History– Travel

• amoebiasis, typhoid fever, malaria, Schistosomiasis

– Residental area• malaria, leptospirosis, brucellosis

– Occupation • farmers, veterinarian, slaughter-house workers =

Brucellosis• workers in the plastic industries = polymer-fume

fever

– Contact with domestic / wild animal / birds : • Brucellosis, psittacosis (pigeons),

Leptospirosis, Q fever, Toxoplasmosis– Diet history

• unpasteurized milk/cheese = Brucellosis

• poorly cooked pork = Trichinosis– Sexual orientation = HIV, STD, PID– Close contact with TB patients

EXAMINATION• General

Calm, conscious, oriented to time, place and person

Ill/not illBuilt/Weight loss (chronic illness)VitalsCLIPJES(Skin rash)

HEAD AND NECK• Feel temporal arteries (tender & thicken)• Eyes – iritis/conjuctivitis (ct disease –

reiter syndrome)• Jaundice (ascending cholangitis)• Fundi – choroidal tubercle (miliary tb),

roth’s spot (ie) and retinal haemorrhage (leukaemia)

• Lymphadenopathy

FACE AND MOUTH• Butterfly rash• Mucous membranes• Seborrhoic dermatitis (HIV)• Mouth ulcers (SLE)• Buccal candidiasis• Teeth & tonsils infection (abscess)• Parotid enlargement• Ears – otitis media

HANDS

• Stigmata of Infective Endocarditis• Vasculitis changes• Clubbing• Presence of arthropathy• Raynaud’s phenomenon

ARMS

• Drug injection sites• Axillary nodes (lymphoma, sarcoidosis,

focal infection)• Skin

CHEST

• Bony tenderness• CVS – murmurs (ie atrial myxoma), rubs

(pericarditis)• Resp – signs of pneumonia, TB, empyema

and lung ca

ABDOMEN• Rose coloured spot

(typhoid fever)• Hepatomegaly

(hepatic ca, alcoholic hepatitis)

• Splenomegaly (haemopoietic malignancy, malaria)

• Renal enlargement

(renal cell ca)• Testicular

enlargement (seminoma)

• Penis & scrotum – discharge/rash

• Inguinal ligament

• Per rectal exam – mass/tenderness in rectum/pelvis (abscess, ca, prostatitis)

• Vaginal Examination – collection of pelvic pus/ Pelvic Inflammatory Disease

CENTRAL NERVOUS SYSTEM

• Signs of meningism (chronic tb meningitis)• Focal neurological signs (brain abscess,

mononeuritis multiplex in polyarteritis nodosa)

STAGE 1: LAB INVESTIAGTIONSStage 1: (screening tests)

1. Full blood count (evalute anaemia, +nce of blasts, thrombocytopenia)

2. ESR & CRP

3. LFTs

4. Blood culture

5. Serum virology (EBV,CMV)

6. M/b panel (LFT,LDH,creatinine)7. Urinalysis and

culture8. Sputum culture and

sensitivity9. Stool and occult

blood10. CXR11. Mantoux test

STAGE 2: LAB INVESTIGATIONS1. Repeat history and

examination

2. Protein electrophoresis

3. CT (chest, abdomen, pelvis)

4. Autoantibody screen (ANA, RF, ANCA, anti-dsDNA)

5. Echocardiography

6. Bone scan(osteomye.)

7. Lumbar puncture8. Consider PSA, CEA9. Temporal artery

biopsy10.HIV test counselling

STAGE 3: LAB INVESTIAGTIONS

1. Bone marrow aspiration

2. Biopsy

3. Bronchoscopy

4. Exploratory laprotomy

STAGE 4: TREATMENT

• Continued observation and examination

• Therapy based on probability of various causes of fever in that setting

• Avoid shotgun empirical approach• Antibiotic??- mask infection

Indication for immediate empirical therapy

• Vital instability• Neutropenia• Nosocomial- if bacteremia, fungemia or

persistently high viral loads are a threat• Cirrhosis, asplenia, immunosuppressive

drug use, exotic travel, environmental exposures

• change IV lines(culture), drugs stopped for 72 hours and empirical therapy started

• Vancomycin (MRSA) with piperacilin/tazobactum(broad spectrum gram negative)

• Granulomatous hepatitis or positive TST- therapeutic trial for TB upto 6wks

• Glucocorticoids and NSIADS- trial only after ruling out any infections. Dramatic response in autoimmune diseases.

Last resort- if fever continues uptil 6 mnths

Initiation of empirical therapy • Doesnot mark end of treatment• Rather it commits physician to more • Thoughtful• Reeaxamination and• Evaluation

HAPPY EARTH DAY

Thank you