Fever of unknown origin: case presentation

A 19 year old university student was admitted to our hospital with history of high grade swinging temperature up to 39°C. She had had a sore throat, which lasted for a few days, accompanied by fever, rigors, and myalgia. Her general practitioner prescribed amoxicillin, and she subsequently developed a macular rash on her wrists, back, and legs associated with the fever spikes. The symptoms were persistent over three weeks, prompting referral to our department. She had travelled to Italy recently and recollected being bitten by mosquitoes. She had no history of recreational drug use or sexual contact and she was not taking any regular medication.

On initial examination she was tachycardic (100 beats/minute) and febrile (37.5°C) with a blood pressure of 108/68 mm Hg. Her oral cavity and cardiovascular, respiratory, abdominal, and nervous system examinations were normal. There was no lymphadenopathy. Her right knee was tender but she had no swollen joints. Chest radiography and abdominal ultrasonography showed no abnormality. The box lists the results of other investigations.

Results of laboratory investigations

White cell count 16.9×10⁹/l (normal range 4-11) with predominant neutrophilia

C reactive protein 326 (normal 0-10) mg/l

Liver function tests: alanine transaminase 65 (5-55) IU/l, γ glutamyltransferase 227 (12-43) IU/l, alkaline phosphatase 127 (30-115) IU/l

Normal antistreptolysin O titres

Negative blood film for malarial parasites

Negative results for mononucleosis spot test, IgM for Epstein-Barr virus, cytomegalovirus polymerase chain reaction, hepatitis B surface antigen, and serology for hepatitis C, chlamydia, and brucella

Autoantibody screen negative (rheumatoid factor, antinuclear antibody, double stranded DNA, extractable nuclear antigen, and antineutrophil cytoplasmic antibodies)

Complement: C3 0.38 (0.8-2.0) g/l, C4 0.1 (0.16-0.4) g/l, cryoglobulins negative

Questions

1. What differential diagnoses would you consider?

2. What further investigations should be carried out?

3. What would you tell the patient and her parents given that tests have not revealed a clear diagnosis at this stage?

Please respond through bmj.com, remembering that this is a real patient and that she and her carers may read your response.

Blood was sent for culture and she was given parenteral cefuroxime. Preliminary blood cultures raised the suspicion of Gram positive organisms. These later grew coagulase negative staphylococcus. She was prescribed teicoplanin and gentamicin at this stage, but staphylococcus was later thought to be a contaminant. Throat swab culture, fungal blood cultures, serial bacterial blood cultures, and malarial films gave negative results. Transthoracic and transoesophageal echocardiograms appeared normal. A diagnosis remained elusive, and the patient and her parents were becoming frustrated.