Pyrexia of Unknown Origin Flashcards
Definition of fever
Fever can be defined as any elevation in body temperature above the normal
How does body temperature vary in normal individuals
Varies slightly, up to 0.8 degrees, over any 24 hour period, from a low in the early morning to a high at 4-6pm
What are pyrogens?
Substances which cause fever
Features of pyrogens
May be exogenous e.g. endotoxins of gram negative bacteria or endogenous e.g. cytokines released from host cells in response to infection
How do pyrogens work?
Act by causing elevation of the set point of the hypothalamic thermoregulatory centre which in turn results in vasoconstriction, decreased peripheral heat loss and fever
How was pyrexia of unknown origin (PUO) defined by Petersdorf and Beeson?
A temperature greater than 38.3 degrees on multiple occasions during a period longer than three weeks that defied one week’s evaluation of the patient in hospital
i.e.; Temp > 38.3 Recorded on multiple occasions Present for at least 3 weeks Defied diagnosis after one week hospital evaluation
When is PUO termed classical PUO?
When it develops in the non-compromised host
What is the modern definition of PUO?
Broader definition - no diagnosis after either;
3 outpatient visits
3 days in hospital
One week of outpatient investigation
Forms of PUO
Classical
Nosocomial
Neutropenic
HIV-Associated
Nosocomial PUO
Fever which develops in hospital and is undiagnosed after 3 days of investigation including 2 days of cultures
Neutropenic PUO
Fever in a patient with a neutrophil count of < 500 cells/mm3 which is undiagnosed after 3 days of investigations
HIV associated PUO
Fever in a patient with HIV infection which has been present and undiagnosed for more than 3 days in an inpatient or four weeks in an outpatient
Major causes of PUO
Infection e.g. TB, HIV Neoplasm e.g. lymphoma Collagen disorder Miscellaneous e.g. drug fevers, venous thrombosis Inflammatory e.g. temporal arteritis Undiagnosed
Tumours most commonly associated with PUO
Lymphoma Hodgkin's disease Renal cell carcinoma Hepatocellular carcinoma Leukaemia
Connective tissue disorders most commonly associated with PUO
Temporal arteritis
Systemic vasculitides
Causes of HIV related PUO
Mycobacterium tuberculosis Mycobacterium avium Other mycobacteria Pneumocystis carinii pneumonia Cytomegalovirus Lymphoma Cryptococcosis Leishmaniasis Toxoplasmosis
Assessment of PUO
History
Examination - repeated
Second opinion
Important aspects of history of a patient with PUO
Organised, systematic, open mind, no time pressure
Travel Occupation Drug and sexual histories Ask specifically about chemical exposure and familial disorders Family history Age of onset Pattern of fever Rashes
What might a history of transient skin rash be indicative of?
Diagnosis of connective tissue disease or chronic meningococcaemia
Symptoms described by many patients which are suggestive of febrile illness but not sufficiently specific
Myalgia
Weight loss
Arthralgia
Shivers
Important aspects of physical examination to remember
Nails Oral cavity Skin Lymph nodes Eyes
Initial investigations of PUO
CXR Urinalysis and urine microscopy FBC and differential WCC C-reactive protein ESR Blood cultures if fever is present Urea Creatinine Electrolytes LFTs
Indications for further examination/investigation
Travel to tropical areas New/changing heart murmur Headache/jaw claudication Microscopic haematuria Risk of TB IVDA High risk sexual contact
Further investigation in a patient with travel to tropical areas
Repeated blood films for malarial parasites
Blood films for borrelia and trypano-somiasis
Rickettsial, coxiella, Dengue, schistosoma, filarial and amoebic serology
HIV test
Bone marrow for leishmaniasis
Further investigation in a patient with new/changing heart murmur
Echocardiography
Further investigation in a patient with headache/jaw claudication
Temporal artery biopsy
CT/PET
Further investigation in a patient with microscopic haematuria
ANCA
Renal US
Further investigation in a patient with risk of TB
Contact history, travel and past TB
Sputum culture
Early morning urine culture
Bone marrow and liver biopsies
Further investigation in a patient with IVDA or high risk sexual contact
HIV antibody
Hepatitis B and C serology
When are invasive investigations indicated in PUO?
If diagnosis is not made through non-invasive techniques
Common invasive investigations of PUO
Involves obtaining tissue for culture and histology
Bone marrow examination
Liver biopsy
Laparoscopy
Lung/lymph node/renal biopsy
In-situ hybridisation of biopsy to identify mycobacteria or viral nucleic acid
Diagnostic laparotomy role is decreasing and is rarely necessary
Imaging modalities used in patients with PUO
CT and MRI to identify small abnormalities
Scintigraphy to detect changes due to inflammation/infection
Isotope bone scan to assess suspected bone or joint infection
Ventilation/perfusion scan to assess suspected multiple pulmonary emboli
Radiolabelled ciprofloxacin derivative to differentiate between infection and sterile inflammation
What are CT and MRI dependent on?
Anatomical changes which take time to develop or which may not develop normally in an immunocompromised host
Role of therapeutic trials
Rarely used
Suspected mycobacterial infection - anti-TB therapy
Suspected vasculitis or connective tissue disorder - steroids
Management of patients with PUO
Most cases will be identifies within a week of intensive assessment
Decision must be made for remaining patients as to whether therapeutic trial is necessary
If clinically well - wait and keep situation under review
If clearly unwell - trial of anti-TB therapy or steroids should be considered
When is the chance of unexplained PUO resolving higher?
More likely in younger patients < 35 years than in the elderly
Affect of steroids in PUO
Often improve a fever as well as the patient being well
Response to steroids in a patient with giant cell arteritis or Still’s disease is dramatic and should be seen after 24-72 hours
Outcomes of PUO
Spontaneous resolution - commoner in younger people
May respond to steroids to NSAIDs
Regular re-appraisal required - cause may not be apparent for several months
What is factitious fever?
Situations in which the patient has manipulated the temperature recordings to fabricate the existence of a fever
What is fabricated fever?
Fever which is genuinely present but which has developed as a consequence of self-induced infection e.g. self injection with faeces
Treatment of fabricated fever
Psychiatric management rather than directly confronting the patient
