Pyrexia of unknown origin
- 1. PYREXIA OF UNKNOWN ORIGIN PRESENTED BY: TANVI SINGLA
- 3. 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°F With evening temperatures being higher than the morning If body temp. exceeds normal variation in an individual, that’s called FEVER
- 4. Liebermiester’s Rule: With each degree centigrade rise in body temp. , heart rate increase by 8 per min Except in those diseases where relative bradycardia sets in.
- 5. 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.
- 6. 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. NOSOCOMIAL 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 NEUTROPENIC PUO •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- ASSOCIATED 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
- 7. COMMON CAUSES OF PUO TB being the no. 1 DRUG FEVER
- 9. INFECTIONS Bacterial 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)
- 10. Uncommon •Leptospirosis •Brucellosis •Chlamydia •Rickettsial infections(Q fever, Scrub Typhus, Rocky Mountain Spotted fever)
- 11. •TB meningitis •Spinal TB •Bone and joint TB •Grannulomatous hepatitis •Abdominal TB •Genitourinary TB •Tubercular lymphadenopathy
- 15. AUTO-IMMUNE DISORDERS •SLE •Vasculitis •Adult still’s disease •Temporal arteritis
- 16. MISCELLANEOUS Hyperthyroidism Phaechromocytoma Metabolic disorders DRUG FEVER: •Antimicrobials(Beta lactum antibiotics) •Cardiovascular (Quinidine) •Antineoplastic •Antiepileptic (phenytoin)
- 17. 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???
- 18. NOSOCOMIAL PUO ETIOLOGY Infections Non infectious cause Undiagnosed Others •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
- 19. 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???
- 20. NEUTROPENIC INFECTIONS Patients 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
- 21. HIV – associated PUO HIV Infection as such may be the cause Other secondary causes are: Pulmonary Tuberculosis Pneumocystis Infection Toxoplasmosis Salmonellosis Cryptococciosis Cytomegalovirus infection M. Avium or M. Intracellulare Non-Hodgkin’s Lymphoma Drug induced fever
- 23. HISTORY TAKING History of present illness 1)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
- 24. •Intermittent fever: Daily spikes: Abscesses, TB, Schistosomiasis Twice – 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
- 25. 5) Associated symptoms: • Rigors and chills Bacterial, rickettsial and protozoal disease Influenza, 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
- 26. • 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
- 27. • 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
- 28. • 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
- 29. Family History –Anyone in family has similar problem: TB, familial Mediterranian fever
- 30. • 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
- 31. –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
- 32. EXAMINATION • General Calm, conscious, oriented to time, place and person Ill/not ill Built/Weight loss (chronic illness) Vitals CLIPJES(Skin rash)
- 33. 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
- 34. FACE AND MOUTH • Butterfly rash • Mucous membranes • Seborrhoic dermatitis (HIV) • Mouth ulcers (SLE) • Buccal candidiasis • Teeth & tonsils infection (abscess) • Parotid enlargement • Ears – otitis media
- 35. HANDS • Stigmata of Infective Endocarditis • Vasculitis changes • Clubbing • Presence of arthropathy • Raynaud’s phenomenon
- 36. ARMS • Drug injection sites • Axillary nodes (lymphoma, sarcoidosis, focal infection) • Skin
- 37. CHEST • Bony tenderness • CVS – murmurs (ie atrial myxoma), rubs (pericarditis) • Resp – signs of pneumonia, TB, empyema and lung ca
- 38. 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
- 39. • Per rectal exam – mass/tenderness in rectum/pelvis (abscess, ca, prostatitis) • Vaginal Examination – collection of pelvic pus/ Pelvic Inflammatory Disease
- 40. CENTRAL NERVOUS SYSTEM • Signs of meningism (chronic tb meningitis) • Focal neurological signs (brain abscess, mononeuritis multiplex in polyarteritis nodosa)
- 41. STAGE 1: LAB INVESTIAGTIONS Stage 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 culture 8. Sputum culture and sensitivity 9. Stool and occult blood 10. CXR 11. Mantoux test
- 42. STAGE 2: LAB INVESTIGATIONS 1. 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 puncture 8. Consider PSA, CEA 9. Temporal artery biopsy 10.HIV test counselling
- 43. STAGE 3: LAB INVESTIAGTIONS 1. Bone marrow aspiration 2. Biopsy 3. Bronchoscopy 4. Exploratory laprotomy
- 46. • Continued observation and examination • Therapy based on probability of various causes of fever in that setting • Avoid shotgun empirical approach • Antibiotic??- mask infection
- 47. 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
- 48. • change IV lines(culture), drugs stopped for 72 hours and empirical therapy started • Vancomycin (MRSA) with piperacilin/tazobactum(broad spectrum gram negative)
- 49. • 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
- 50. Initiation of empirical therapy • Doesnot mark end of treatment • Rather it commits physician to more • Thoughtful • Reeaxamination and • Evaluation
- 52. HAPPY EARTH DAY Thank you