Makindo Medical Notes

Related Subjects: |Fever in a traveller |Malaria Falciparum |Malaria Non Falciparum |Viral Haemorrhagic Fevers (VHF) |Lassa fever |Dengue |Marburg virus disease |AIDS HIV |Yellow fever |Ebola Virus |Leptospirosis | Crimean-Congo haemorrhagic fever |African Trypanosomiasis (Sleeping sickness) |American Trypanosomiasis (Chagas Disease) |Incubation Periods |Notifiable Diseases UK

A case in which to take several expert opinions as one works through the differential diagnoses noting that not all pyrexias have an infective cause. Current definition: a documented fever persisting for >2 weeks, with no clear diagnosis despite intelligent and intensive investigation.

About

• The original definition from the early 1960s before modern CT/MRI/Ultrasound by Petersdorf and Beeson suggested that the persisting fever more than 38.3°C was present over a 3-week period with no obvious cause despite inpatient tests for one week.
• Current definition is 2 weeks of fever with no clear diagnosis despite intelligent and intensive investigations
• Fever is a product of cytokines and interferons and depends upon an able immune response to happen. There must obviously be an evolutionary benefit for us to produce a fever in response to infection but some patients on steroids or elderly or immunoparesed may not mount a fever even with severe sepsis.
• Fever usually occurs when a pyrogen such as a microbial toxin, microbe particle, or cytokine resets the hypothalamus to a higher temperature

Definition

• Current: Fever persisting for more than 2 weeks period with No clear diagnosis despite intelligent and intensive tests
• Original: Fever persisting > 38°C persisting for > 3 wks with no diagnosis after initial investigation.

Differential

• Infection (TB), Endocarditis, Urinary or chest infection
• Pyogenic Abscess - pelvic, abdominal, renal, epidural, chest, spinal
• Malaria, Amoebiasis, Leishmaniasis, Trypanosomiasis
• Toxoplasmosis, EBV/CMV, Brucellosis, Lyme, Whipple's, HIV
• Rickettsia - Typhus, Q fever
• Connective tissue disease, Vasculitis (SLE, GCA, PMR, RA, Adult Stills)
• Familial Mediterranean Fever and related
• Malignancy, Drugs, Atrial myxoma, Thyrotoxicosis,

The important aspects

• A very focused and detailed history - travel, drugs, IV drugs
• A comprehensive examination - top to toe.
• Check every centimetre of skin back and front.
• Don't omit PV and PR exam and testes and perineum and mouth and teeth
• Imaging of those places that cannot be easily examined
• Looking for Infection, Malignancy and Connective tissue disease
• Repeating the above regularly until cause found
• Take early advice - cardiologists, haematologists, rheumatologists. microbiologists etc

Investigations

• FBC + Differential (Increased neutrophils and bacterial infection), ESR, CRP, LFT's, U&E, TFT's
• Baseline sera e.g. EBV, CMV, HIV, Bartonella, Toxoplasma, Brucella, Lyme disease
• Chlamydia, salmonella, Borrelia recurrentis, Q fever, leptospirosis.
• Blood / Urine / Stool cultures x 3
• Chest X-Ray and Tuberculin test
• Rheumatoid factor, Antinuclear antibodies, Vasculitis screen
• Echocardiogram: for infective endocarditis or atrial myxoma.
• Malaria: Repeated thick and thin blood films, antigen testing.
• CT or USS Abdomen /pelvis: malignancy, abscess, PID
• HIV test, Hepatitis screen, Syphilis serology
• Liver biopsy and Bone marrow biopsy for leukaemia or culture for miliary TB
• Stool for ova cysts and parasites and culture and sensitivity
• Wounds: swab for cultures
• White cell scan: abscess, empyema or osteomyelitis.
• Bone scan for osteomyelitis or metastatic bone disease.
• MRI for osteomyelitis
• Liver biopsy: May reveal TB, lymphoma or granulomatous disease, including sarcoidosis.
• Bone marrow biopsy: Has a diagnostic yield in PUO of ~15%, the most commonly detected diseases being myelodysplasia, other haematological malignancies and TB. Brucellosis, enteric fever or visceral leishmaniasis.
• Temporal artery biopsy: Should be considered in patients > 50 yrs, even if the ESR is not significantly elevated. Needs at least 1.5 cm section of artery is biopsied as skip lesions

List of causes

Management

• Try to avoid blind treatment but usually the patient has been treated with broad-spectrum antibiotics prior to a referral which muddies the waters greatly. Get a second opinion. Two heads often better than one. Repeated examination and history - travel, sex partners, work.
• Unless the patient is septicaemic or deteriorating it might be best to stop all and watch and wait and see what develops following good senior advice. Then send all cultures again.
• Consider stopping drugs not needed. Well patients may be monitored as an outpatient. These are good cases for getting second opinions on if the cause by definition seems elusive or multiple.