Fever of unknown origin: case presentation

1.What differential diagnoses would you consider ?

A/ Still's disease, adult type/most probable diagnosis/

B/ Osteomyelitis /less likely/

C/ Another collagen disease /less likely/

D/ Malignancy /highly unlikely, thank God/

2. What further investigations should be carried out ?

It seems to me that this young lady has been thoroughly and
meticuously investigated. There are not many, if at all any test(s) that
have not been done. Looking at the all the investigations ordered and done, she
was probably initially admitted under Infectious Disease team. They did
rule out most of the infective causes. It must be probably them who started
IV antibiotic treatment on the background of what was initially looking as
a positive blood culture. Most of other potential causes (malignancy, collagen vascular disease) have been almost ruled out as
well. Internal Medicine team seems to be very good and well coordinated in
that hospital. I have feeling that Rheumatology team made important input
to the final diagnosis for this young lady.

The only test that I would consider adding is X-ray of the right knee
joint and distal femur. Just to rule out osteomyelitis or any other
unexpected joint/bone problem in that area that is already clinically
tender.
ESR will definitely be high and I would not be pushing very hard for it. I
do not think joint aspiration is necessary.

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

I would tell them that at this stage the definitive diagnosis is not
clear yet. However, their daughter may be having rare type of disease
called Still's disease. But before we definitely confirm it as a such (this is diagnosed after other disease are excluded), it is important to
get joint opinion from Rheumatology and Infectious Disease team. The
answer is probably somewhere there....

Competing interests:
None declared

19 F with fever, raised inflammatory markers and hypocomplementemia-
Differential diagnosis here are-

1. Immune complex disease- SLE or glomerulonephritis

2. Most common infections have been ruled out- however consideration
should be given to tuberculosis, intrabdominal collections and pelvic
inflammatory disease, gonorhoea etc (sexual hx should be taken again)

3. Lymphomas

4. Adult onset Still's disease (cannot explain low complement levels)

Investigations suggested-

1. Urine for microscopy and culture

2. Cervical culture

3. CXR

4. CT scan abdomen/Pelvis

5. Ferritin

Obviously distressing time for everyone but would not discuss cancer
at this stage.

Competing interests:
None declared

if in doubt sbe, stop antiobiotics, repeat echos

Competing interests:
None declared

In essence this is a 19 year old girl with:

Persistent fever, transient rash and monoarthralgia.

Elevated acute phase reactants ( C-Reactive Protein, Neutrophilia).
Raised Gamma Glutamyl Transferase(GGT) with otherwise normal liver
function.
Low complement levels.

Differential Diagnosis:

Running this across the classical diagnostic sieve:

1. Infection: Most of the common infections have been ruled out.
Others that could be considered include:

• Tuberculosis: not a typical clinical picture and no h/o contact ,
but needs to be considered.

• A mild case of “chronic” meningococcemia cant be ruled out,
although 3 weeks is long enough for the disease to either worsen or
resolve

• Rubella: fever, rash and arthralgia , but rash not typical
.Prolonged fever unlikely.

• Hepatitis/Cholangitis; could explain fever and elevated GGT, but no
abdominal symptoms or jaundice.

• Some cases of Enteric fever may not have positive blood cultures.

Other “exotic” infections don’t seem to fit the bill.

2. Connective tissue/auto-immune disease:

• Juvenile Rheumatoid Arthritis is a strong possibility. The
evanescent rash is typical. However conventional wisdom dictates that when
there is rash, there is usually polyarthralgia.

• Systemic Lupus Erythematosus(SLE): Also a strong contender. The
altered liver function and the low complement levels are consistent with
SLE.

• Auto-immune Hepatitis

• Sclerosing cholangitis: can explain fever and altered GGT.

3. Immune deficiency: Possible coagulase-negative staphylococcal
sepsis in association with low complement levels warrant further testing.

4.. Maligancies: Hodgkins and pre-leukaemic leukaemia can present
like this with a normal blood film as can some renal tumours

5. Endocrine: Thyrotoxicosis should be considered in view of
tachycardia. Can be associated with auto-immune diseases

6.. Others: Familial Mediterranean fever

Juvenile Rheumatoid Arthritis (Systemic Onset) and SLE are highest on
the list of possibilities.

Further investigations:

1. ESR

2. PCR for Meningococcus

3. Mantoux Test

4. Urine dipstick /microscopy to look for haematuria/casts.

5. Renal function tests

6. Thyroid Function Test

7. Chest X ray

8. Abdominal Ultrasound.

9. Immune studies:A repeat auto-immune screen , also looking at anti-LKM
antibodies;

10. Complement pathway and immunoglobulins

11. If remains febrile: Bone marrow aspirate may be considered. Bone
marrow can also be cultured for Salmonella

What to tell the patient/parents

This is obviously a distressing time for the patient and her parents.
I would tell them that many of the common causes of fever have been ruled
out and that we are giving her adequate antibiotic cover for most of the
bacteria. We might need to do more specialised tests to find out the exact
cause. As always this is more likely to be an uncommon presentation of a
common disease than vice versa. If all tests are negative, a bone marrow
aspiration may have to be considered. Possibility of occult malignancy,
though frightening has to be mentioned.

Competing interests:
None declared