Pyrexia of Uknown Origin Flashcards
What is normal temperature?
36.0-37.7 degrees
Why is aural temperature slightly lower than oral and rectal temperature?
-Circadian variation lowest in morning
-Physiological variation
-Sweating due to endocrine causes (thyroid) or medications or feeling ‘hot’ not same as fever
What is Faget’s sign?
-Pulse rate rises approx. 10 bpm per degree
-Some infections associated with pulse fever dissociation
=Typhoid, brucellosis, Legionnaire’s disease
Pathogenesis of fever
-Trigger: pyrogen (PAMP, damage associated molecular patterns/ exogenous and endogenous)
-Pattern recognition of innate immune system (Toll)= signal transduction= cytokines
=IL1/6, hypothalamus generates cAMP
=Rest body temperature
-Sympathetic NS- noradrenaline release
-Thermogenesis in brown adipose tissues, vasoconstriction in periphery, metabolic rate raised through muscle contraction (shivering)
Causes of fever
-Infection
-Malignancy
-Tissue injury, thrombosis, infarction
-Inflammatory conditions (rheumatological)
-Medications
History approach to patient with undifferentiated fever
-Presenting symptom (fever features/ not just hot or cold)
-Associated symptoms (e.g., cough and sputum, organ system?)
-PMH (diabetes, immunosuppressants= susceptibility to infection?)
-Epidemiological risk factors for infections
-Symptoms to suggest focus of infection
Epidemiological risk factors for infections
-Age, gender, occupation
-Travel history
-Sexual history
-Animal exposure, hobbies, dietary risk factors
-Recent antibiotic treatment
Symptoms that suggest a focus of infection (examination findings)
-Skin rash or infection, splinter haemorrhages
-Cough or chest pain/ crackles, pleural effusion, new murmurs (infective endocarditis)
-Urinary symptoms
=Dysuria, frequency, haematuria
-Headache, sore throat, myalgia
-Abdominal or loin tenderness, masses
-Neck stiffness, confusion
-Pus on tonsils, lymphadenopathy
-Diarrhoea
-Nonspecific sign like UTI
Non-specific tests to assess likelihood/ severity of infection
-Full blood count
=Neutrophilia
=Lymphopenia or lymphocytosis
=Raised platelet count
-ESR
-CRP
Supportive tests to facilitate management
-Urea (renal function, low BP)
-Electrolytes
-LFT (hepatic origin?)
-Calcium
-Albumin (negative base reactant, reduced in a cute response to fever so systemic response)
Specific tests to elucidate cause of fever
-Blood cultures: several sets
-Urine culture (usually mid-stream)
-Sputum culture
-Stool culture
-Throat swab for (viral) PCR
-Chest x-ray (exclude pneumonia)
-Brain imaging and lumbar puncture and CSF examination
Liver function test results
-Very high ALT? Viral hepatitis, CMV
-Raised alkaline phosphatase? =Obstructive/ Cholecystitis
-Moderate rise in ALT (most infections)
-Reduced albumin (a negative acute phase reactant) = a sign of severity and? chronicity
Syndromic approach to guide investigations
-Rash
-Lymphadenopathy
-Fever and jaundice
-Hospital associated fever
-Respiratory tract infections
-Cardiovascular
-Travel
-Drug fever
Rash causes
- Childhood exanthems e.g. measles
- Herpes viruses ; HSV, VZV, EBV, CMV
- Enteroviruses
- HIV
- Neisseria meningitidis
- Toxic shock syndrome
- Syphilis
- Rickettsial illnesses (travel)
- Lyme disease
- Still’s disease (rheumatological)
Lymphadenopathy causes
Streptococcal infection
* EBV, CMV, toxoplasma
* HIV
* Tuberculosis
* Syphilis
* Lymphoma
* Carcinoma
* Sarcoid
Fever and jaundice causes
Viral hepatitis
* Cholangitis
* Bacterial sepsis
* Hepatic abscess
* Leptospirosis
* Drug toxicity
* Auto-immune hepatitis
* Malignancy
Hospital associated fever causes
- Hospital associated
pneumonia - Vascular catheter infection
- Urinary tract infection
- Surgical wound infection
- Thromboembolism
- Drug or transfusion
reaction
Respiratory tract infections cause
- Viral upper respiratory tract infection
- Streptococcal pharyngitis
- EBV
- Community-acquired pneumonia
- Pleurisy and empyema
- Tuberculosis
- Pulmonary emboli
Cardiovascular causes
- Endocarditis
- Pericarditis
- Myocarditis
- Atrial myxoma
- Thrombo-embolic disease
Travel causes
- Malaria
- Dengue
- Typhoid
- Dysentery
- Thrombo-embolic disease
Drug fever causes
- Antimicrobials
- Non-steroidals
- Allopurinol
- Phenytoin, carbimazepine and
anti-seizure meds - Selective serotonin reuptake
inhibitors - Chemotherapy e.g. bleomycin
Fever with joint pain causes (arthralgia)
-Single joint
=Septic arthritis, secondary to bacteraemia
=Endocarditis with embolic phenomena
=Gonococcal infection
=Lyme disease
=Gout or pseudo-gut
-Osteomyelitis
-Discitis (back pain)
-Polyarticular
=Viral infections; exanthems (especially Parvovirus B19, Hep B)
=Rheumatological disorders (RA)
Serology findings
-Useful and should be considered on all admissions with
fever; especially when high background incidence
=HIV, Hepatitis B and C
-Appropriate when multisystem symptoms, pharyngitis
or lymphadenopathy in young adults
=Epstein Barr IgM, CMV
-Reserved for particular epidemiological settings
=Coxiella burnetii, Brucella species, Leptospirosis species
Investigation of persistent fever
-Revisit history
-Repeat initial investigations
=Blood and urine culture
-Imaging
=Chest X ray
=Abdominal imaging
=USS
=CT
What is USS used for?
-Cheap and available
-Good for solid organs of upper abdomen
-Less good for bowel, retroperitoneum
What is CT used for?
-Pelvic/ lower abdominal abscess (diverticular abscess)
-Retroperitoneal lymph nodes (malignancy, TB)
Fever in immunocompromised hosts
-May have less obvious inflammation (masking signs like meningism, radiological appearances like infiltrates on CXR)
-Infectious syndromes
-Chemotherapy induced neutropenia
-Transplantation, HIV (not receiving antiretroviral therapy), high dose steroids, T-cell defects
-Hypogammaglobulinemia
-Asplenic (encapsulated bacteria)
-Anti-TNF therapy (mycobacterial disease)
Causes of chemotherapy induced neutropenia
-Neutropenic fever
-Catheter-related infections fungal infections
-Underlying haematologic malignancy
-Side effects of chemotherapy
Transplantation infections
-Pneumocystis pneumonia
-Cryptococcal infection
-Toxoplasma encephalitis
-Herpesvirus infections
-Mucosal candida infections
-Mycobacterial infections
Causes of hypogammaglobulinemia
-Bacterial sino-pulmonary infection
-Giardiasis
-Chronic enteroviral infections
-Gastrointestinal tract
lymphoma
-Auto-immune phenomena
Asplenic causes
Infections with encapsulated bacteria e.g. Pneumococcus, Haemophilus influenzae
What is classified as fever of unexplained origin?
-Fever >38.3 degrees for >3 weeks
-Diagnosis uncertain after investigation for:
=3 out-patient visits
=3 days investigation in hospital
=One-week ambulatory investigation
Usual cases of pyrexia of unknown origin
-Infection
-Neoplasm
-Connective tissue disorders
-Multisystem
-Miscellaneous
-Unknown
Sub-groups to PUO
-Classical
-Nosocomial (hospital associated causes)
-Immunodeficient
-HIV
Which tests were most useful in the investigation of PUO?
-Abdominal CT scan (“19%”)
=Intra-abdominal abscess
=Lymphoproliferative disorders
-Liver biopsy (“15%”)
-Temporal artery biopsy in the elderly (temporal arteritis)
PUO changing practice
-Better molecular diagnostics
-PCR for 16S ribosomal RNA for detection and
identification of bacteria
-Better autoimmune serology
=Anti-CCP2 antibodies instead of rheumatoid factor
-Better radiology
=PET scanning
