Fortbildungen / Formations continues 2012 - IUMSP

staphylococcus aureus. The venous Hickman-catheter was
replaced each time, the last time about two years ago.
About six month ago, our patient was admitted to our
hospital with fever of unknown origin, headache, clinically
no signs of infection, especially no signs of an intestinal
infection. A broad-spectrum antibiotic therapy was
installed. Central and peripheral blood-cultures stayed
negative. The fever dissolved within a few days and our
patient was dismissed. After this �rst period, recurrent
episodes with fever of unknown origin and headache followed.
Each time the episodes worsened with the development
of a bicytopenia, hyperferritinemia, hepatopathy,
hypoproteinemia and coagulopathy. Under a broad-spectrum
antibiotic therapy, in all episodes, the fever and the
symptoms dissolved within a few days. The blood cultures
stayed sterile and serological no pathogens were found.
However in the skin smear around the gastric tube and in
the gastric juice, repeatedly during the third and fourth
episode different candida species, E. coli and enterobacter
cloacae species were found. The relevance of these �ndings
was questioned by us. Could the fever episodes be
triggered by a bacteremia through an intestinal bacterial
or fungal overgrowth? Nevertheless we implemented
gut decontamination with oral rifaximin and vancomycin
and an antifungal therapy and prophylaxis was installed.
Although discussed controversial in the literature, we
stopped the child’s lipid infusion in his parenteral nutrition,
but did not see any effect on the course of his fever.
As during the recurrent episodes, our patient
showed more and more signs for a hemophagocytic
lymphohistiocytosis,we performed during the fourth episode
further investigations for HLH, which showed the
following results: The �owcytometer analyses showed a
leuko- and lymphopenia with a normal distribution of
T-, B-, and NK-cells. HLA-DR expression of the CD4
and CD8 T-lymphocytes was normal, so was the perforin
expression of the T-lymphocytes and the NK-cells.
The sCD25 interleukin receptor and sCD163 were both
elevated with 1669IU/ml respectively 1519ng/ml. Bone
marrow aspirate showed a massive increase of histiocytes
not typical for HLH, some with phagocytosis of erythrocytes
and granulocytes. Erythropoiesis was decreased, so
was the granulopoiesis. No signs of malignancy. The hair
bole analyses did not show any signs for a perforin defect.
As according to the HLH diagnostic criteria only four
symptoms were present (fever, bicytopenia, hyperferritinemia
and hypo�brinogenemia), the diagnosis of an acquired
or genetic form of HLH could not be made.
The last time the boy was admitted to our hospital, his
symptoms at �rst did not seem very different than in all
previous episodes. He presented with fever more than
40°C and malaise. The physical examination showed a
pale boy complaining about headache, lacking infectious
SPOG
signs. Solely the skin around his gastric tube seemed
slightly irritated and several non-painful lymph nodes
were palpated cervical, the largest measuring around 3cm
in diameter. His initial blood count revealed a tri-cytopenia
with low hemoglobin, platelets and leukocytes, clotting
disorder without bleeding signs, elevated C - reactive
protein, transaminases and ferritin. Blood cultures,
skin smears around the gastric tube, gastric juice, and
urine were taken. We started a broad-spectrum antibiotic
therapy with meropenem. The skin smear showed
an infection with Brevundimonas vesicularis and out of
the gastric juice Candida lusitaniae was isolated. According
to the resistance pattern of the candida the antifungal
therapy was changed. During the course of the next days
the boy stayed febrile, and developed a splenomegaly of
3 cm below the costal margin. The hemoglobin (94g/l),
leucocytes (1.96G/l), ANC (580) and platelets (56 G/l)
sunk further, so did the Quick (33%, INR 2.0), and the
�brinogen till a measured minimum of 1.0 g/l. The C -
reactive protein (131mg/l), transaminases (564/80 U/l)
and ferritin (40772ug/l) increased further. The lipid infusion
was stopped due to the hepatopathy and for the �rst
time we measured elevated triglycerides with a maximum
of 8.73mmol/l. So this time according to the diagnostic
criteria of HLH enough criteria (�ve out of eight) were
ful�lled to make the diagnosis of an acquired HLH (Fever,
tri-cytopenia, splenomegaly, elevated �brinogen, ferritin
and triglycerides).
So we installed a therapy with i.v. immunoglobulin G
(0.5g/kg/dose) on two following days. The next two days
the fever vanished, before our patient was febrile again on
the third day after the application of immunoglobulins.
Still not completely convinced of a non-infectious cause of
the fever, we augmented the antibiotic therapy by adding
vancomycin, but also the anti-in�ammatory therapy by
adding prednisolone (2mg/kg/day) for seven days. On the
third day of the steroid therapy the fever dissolved and the
laboratory �ndings slowly normalized. A recovery due to
the anti-in�ammatory therapy or due to the antibiotic-
and antifungal therapy? During the whole time of the
hospitalization, our patient’s condition was never critical
or extremely bad. Only during the fever peaks he complained
about headache and had to vomit several times,
without complaining about abdominal pain.
On the day of the planned discharge from the hospital
the Hickman-catheter was by chance displaced and had to
be removed. The surgeon reported that the two year old
Hickman-catheter was completely fragile and crumbly.
Since this catheter was removed our patient did not show any
further episodes of fever with a hyperin�ammatory response.
Discussion
In the presented case, our patient showed the symptoms
of an overreacting immune system with fever, cytopenia,
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