Fever of unknown origin: case presentation

Very briefly, a young female, with a three week history of high
fevers, a previous sore throat, a rash, single joint involvement with
constitutional upset, an inflammatory response associated with low C3
greater than low C4, neutrophilia, slightly deranged liver enzymes and a
travel history.

Differential diagnosis and further investigations include:

1. Adult-onset Still’s disease (serum ferritin).

2. SLE (dsDNA and ANA negative; anti-Ku and anti-C1q antibodies could be
measured).

3. Infective endocarditis (cannot exclude this and repeat TOE and TTE
should be performed; ECG abnormalities such as prolonged P-R interval?).

4. Reactive arthritis (any GI/GU symptoms? Stool and cervical cultures
should be sent, including for oocytes, cyst and ova).

5. Vasculitis associated with a low complement (mixed essential
cryoglobulinaemia, HCV-associated (could perform HCV PCR),
hypocomplementaemic urticarial vasculitis (anti-C1q antibodies),
poststreptococcal glomerulonephritis, mesangiocapillary glomerulonephritis
associated with factor H deficiency or C3 nephritic factor).

6. Lyme disease (bittne; serology; ECG conduction abnormalities).

7. Autoimmune hepatitis (auto-antibodies, e.g., anti-LKM and SMA
antibodies; although ANA was negative).

8. Rheumatic fever (although polyarthritis would be expected).

9. Behçet's disease (any ulceration or eye involvement? Pathergy test
could be performed if higher suspicion. Sometimes associated with low
complement, negative rheumatoid factor; C9 level and CRP are markers of
activity).

10. Haematological malignancy (Waldenström's hypergammaglobulinaemic
purpura can cause low complement and a rash; serum immunoglobulins and
electrophoresis looking for a band or hypergammaglobulinaemia, and urine
BJ protein should be sent off).

Other things to exclude include sarcoidosis (calcium, urine calcium,
ACE), TB (special TB blood cultures, Mantaux, Heaf), HIV (PCR, serology),
Dengue (serology), syphilis (VRDL). Unlikely rarities include familial
Mediterranean fever, hyperimmunoglobulin D syndrome (high IgD and IgA) and
familial Hibernian fever.

The results of more basic tests:

 Renal function?

 Haemoglobin concentration and platelet count?

 ECG abnormalities? e.g., heart block.

 Active urinary sediment or casts?

Family discussions

 I would explicitly discuss the problem with the patient and
her family, making clear the results of all the investigations and the
rationale for further tests.

 The fact that everything that can be done is being done
should be reiterated.

 The fact that a clear diagnosis at this stage has not been
achieved should also be stated but that antibiotics will continue for the
time being to cover infective endocarditis.

Competing interests:
None declared