PYREXIA OF UNKNOWN ORIGIN

DR HONEY SAVLA

DNB MEDICINE STUDENT

(1ST YEAR)

Pyrexia of Unknown Origin (PUO)

Definition:

by Petersdorf and Beeson in 1961

“Temperature higher than 38.3°C (101°F) on atleast two occasions ,

persisting without diagnosis for at least 3 weeks,

no known immunocompromised state,

Diagnosis that remains uncertain after a thorough history taking physical

examination and obligatory investigations.

• Obligatory investigtions include• Esr,crp,platelet count,tlc,hb,electrolytes• Creatinine,total proteins,alkaline

phosphate,alt,ast,ldh,ck,ferritin,ANA,RF,• Protein electrophoresis• Urine analysis• Blood culture (3 times)urine culture,cxr• Usg,skin test.

Approach to patient with PUO

• Stage 1: Careful history taking, physical examination and screening tests

• Stage 2: Review the history, repeating physical examination, specific diagnostic tests & non invasive investigations

• Stage 3: Invasive tests• Stage 4: Therapeutic trials

Stage 1

History taking:

• Occupation

• Personal history

• Exposure to animals

• Travel history

• Past medical history

• Family history

Fever patterns:

• Continuous

• Remittent

• Intermittent

• Tertian ( 48 hrs)

• Quotidian (24 hrs)

• Quartan (72 hrs)

• Saddle back

• Picket fence

Body site Physical finding diagnosis

Head Sinus tenderness sinusitis

Temporal artery nodules & reduced pulsation

Temporal arteritis

oropharynx ulceration Disseminated Histoplasmosis

Tender tooth Periapical abscess

Fundi / conjunctiva Choroid tubercle Disseminated granulomatosis

Petechiae, Roth’s spots Infective endocarditis

Thyroid thyroid enlargement Thyroididtis

Physical examination:

Heart murmur myxomas, endocarditis

Abdomen Enlarged lymph nodes , splenomegaly

lymphomas., disseminated granulomatosis

Rectum Perirectal tenderness Abcess

Prostatic tenderness Abcess

Lower limbs deep vein tenderness DVT & thrombophlebitis

Skin & nail Petechiae, splinter hemorrhages, subcutaneous nodules, clubbing

Vasculitis, endocarditis

Laboratory investigations:

• Complete blood count

• Differential leukocyte count

• ESR/ CRP

• Electrolytes

• Microscopic urine analysis

• Cultures of blood & urine

Stage 2• Review history & repeat physical examination

• Specific investigations

• Repeat sampling of blood & other body fluids.

• Skin tests

• Blood for antibodies – HIV antibodies, CMV

antibodies, EBV antibodies.

• Serological tests for toxoplasmosis, psittacosis and

rickettsial infections, syphillis.

• Serology for rheumatologic disorders like antinuclear

and antineutrophilic cytoplasmic antibodies,

rheumatoid factor

• Quatiferon TB Gold in tube and T spot TB – detects

ϒ interferon release.

Microscopy:

• Direct examination of blood smears: malaria,

trypanosomiasis ,babesia, leishmania, relapsing fever

rat bite fever, ehrlichiosis.

• Intra cellular organisms, bacteria, inclusion bodies,

protozoal amastigotes.

Imaging studies:

• GI contrast study

• High resolution spiral CT

• Arteriography

• Echocardiography

• Duplex imaging

Radionucleotide scanning:

• Flurodeoxy – PET scanning

Stage 3

• Biopsy of liver and bone marrow

• Lymph node biopsy

• Blind biopsy of 1 or both temporal artery in

patient > 50 yrs

• Exploratory laparotomy

MANAGEMENT

• Therapy withheld until cause is found

• Empirical corticosteroids or anti inflammatories in

temporal arteritis.

• Vital sign instability & neutropenia –

Fluoroquinolones + piperacillin,

vancomycin + ceftazidime/cefepime/

carbapenem with or without aminoglycoside,

Management of Nosocomial PUO:

• Change of IV lines, catheters

• Empirical treatment:

Vancomycin for MRSA

Broad spectrum Gram negative coverage

Piperacillin + tazobactum

Ticarcillin + clavulinic acid

Meropenem

Stage 4

Therapeutic trials:

• Empirical treatment with corticosteroids or NSAIDS

or antimicrobials

• Antimycobacterial agents in AIDS & neutropenic

• Blind therapy- delay in correct diagnosis

PROGNOSIS

• Poorest prognosis - elderly & malignant

• Delay in diagnosis affects prognosis of

intraabdominal infections, miliary tuberculosis,

disseminated fungal infections & recurrent

pulmonary emboli

• Undiagnosed PUO for prolonged duration – good

prognosis.

THANK YOU