Pyrexia of unknown origin Flashcards
What is fever?
Fever - Elevation of body temp >37oC
When does pyrexia occur?
- Part of the systemic inflammatory response (Endogenous pyrogens = Cytokines)
- Exogenous pyrogens = Endotoxins from gram negative bacteria
How much does body temperature change throughout a day and due to what?
Variation of up to 0.8oC:
- Lowest in the morning
- Highest in the early evening
- Caused by circadian rhythm
What is a pyrogen?
A substance that acts at the hypothalamic thermoregulatory centre to cause reduced heat loss, leading to fever
What are the sources of pyrogens?
- Endogenous e.g. cytokines
- Exogenous e.g. Endotoxins from Gram-ve bacteria
What is Petersdorf and Beeson (1961) definition of pyrexia of Unknown Origin?
- Temp > 38.3C
- Recorded on multiple occasions
- Present for at least three weeks
- Defied diagnosis after one week of hospital evaluation
What is the modern definition of pyrexia of Unknown Origin?
- 3 outpatient visits; or
- 3 days in hospital; or
- One week of outpatient investigation
Nosocomial pyrexia of unknown origin?
Develops in hospital, undiagnosed after 3 days
Neutropenic pyrexia of unknown origin?
Undiagnosed fever in patient with neutrophils <500/mm3
HIV-associated pyrexia of unknown origin?
Fever in a patient with HIV infection - present and undiagnosed fro more than 3 days in an inpatient or 4 weeks in an outpatient
What is the most common cause of pyrexia currently?
Unknown cause, 51%
What is the second most common cause of pyrexia currently?
1) Inflammatory cause, 22%; followed by,
2) infection, 16%; followed by
3) malignancy, 7%
What is the second most common cause of pyrexia in 1950s?
Infection
What is the most common causes of HIV-related pyrexia of unknown origin
1) Mycobacterium tuberculosis, 21%
2) More than one causative disease
3) Mycobacterium avium, 18%
4) Unknown, 16%
How to assess someone with pyrexia of unknown origin?
1) History - Travel, occupation, hobbies, family history, past medical and surgical history, drug history, pattern of fever
2) Examination (Be thorough) - Skin, eyes, oral cavity, nails and lymph nodes
- Repeating examinations is often worthwhile
Which simple investigations for someone with pyrexia of unknown origin?
- Chest X-Ray
- Urinalysis and urine microscopy
- Full blood count and differential white cell count
- C-Reactive Protein and Erythrocyte Sedimentation Rate
- Blood cultures taken at times of fevers
- Urea, creatinine, electrolytes, liver function tests
Which investigation(s) for someone with pyrexia of unknown origin who has recently travelled to a tropical region?
Blood - Malarial parasites, dengue, HIV,
Bone marrow - Leishmaniasis
Which investigation(s) for someone with pyrexia of unknown origin who has a new murmur?
Echocardiography
Which investigation(s) for someone with pyrexia of unknown origin who is suffering headaches?
Temporal artery biopsy
Which investigation(s) for someone with pyrexia of unknown origin who has micro haematuria?
Auto-antibodies +/- renal biopsy (polyarteritis)
Renal Ultrasound
Which investigation(s) for someone with pyrexia of unknown origin who has had TB contact?
Sputum smear
Bone marrow
Mantoux
Which investigation(s) for someone with pyrexia of unknown origin who has has drug misuse?
Screen for blood-borne viruses
What is the issue with imagine in unknown pyrexia?
Cannot always differentiate between infection and inflammation
Anatomical changes may not develop n those who are immunocompromised
What imaging techniques are used in pyrexia of unknown cause?
1) CT-PET (Positive emission tomography) Using FDG (Fluorodeoxyglusose marker)
2) CT
3) Ultrasound
Which invasive investigations are used in pyrexia of unknown causes?
- Obtain tissue cultures and histology
- Bone marrow and liver often examined as part of blind investigation (Malignancy, TB, lymphoma)
- Diagnostic laparotomy (Rarely)
Which treatments are used in pyrexia of unknown causes?
1) Therapeutic trial:
- Rare
- Anti-tuberculosis therapy - response usually within two weeks if the cause
- Steroids for a vasculitis response usually within 48hrs if the cause
What is a fabricated fever?
Fever is real but self induced:
- Self injection is common
- Microbiology is often strongest clue
- Patient often continues even when very sick
When there is fabricated fever what should be done?
Psychiatric consultation rather than direct confrontation
Who is more likely for spontaneous resolution of pyrexia of unknown cause?
The young versus the elderly
