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First Author: Nikhil A. Patel, Mayo Medical School, Class of
Introduction: In adults, fever of unknown
origin (FUO) is primarily infectious, neoplastic, or autoimmune in
etiology. It is characterized by a prolonged febrile illness
without an established etiology despite intensive evaluation and
diagnostic testing. When the history, examination, or imaging
uncovers a possible source, specific testing should be performed.
Biopsy is a specific and critical modality in the directed
evaluation of FUO especially when thrombocytopenia and anemia are
present. Therapeutic trials of antimicrobials or glucocorticoids
are tempting but rarely establish a diagnosis.
Case Description: A 69-year-old South Sudanese
woman presented to outside hospital with fever and productive
cough. She was diagnosed with sepsis secondary to streptococcus
pneumonia by urine antigen. She responded to fluid resuscitation
and was kept on levofloxacin to complete a 7 day course after
dismissal from the hospital.
Two weeks later she presented again with similar symptomology
along with anemia and thrombocytosis. This time she continued to
deteriorate despite multiple IV antibiotics and required ICU level
of care. Extensive infectious disease workup yielded only a
positive QuantiFERON-TB test and a negative HIV antibody assays. CT
of abdomen and pelvis revealed mesenteric lymphadenopathy and
bilateral axillary lymph adenopathy. Right axillary lymph node
aspiration was performed but was nondiagnostic. CT/PET scan again
showed persistent mesenteric and axillary lymphadenopathy as well
as a hypermetabolic spleen. Excisional biopsy pathology of right
inguinal lymph node revealed HHV-8 positive, MCD. She was initiated
on rituximab and ganciclovir therapy. For the history of latent TB
infection, she was started on isoniazid with vitamin B6. She
improved dramatically with this therapy and was discharged to
follow up as an outpatient with hematology and infectious
Discussion: Castleman's disease in its
multicentric form is strongly associated with immunosuppression,
HIV, and HHV-8 infection. Despite many cases associated with HIV
infection, non-HIV, HHV-8 positive MCD can also occur. Diagnosis
should be suspected in patients with fever, splenomegaly, and
peripheral lymphadenopathy. CT imaging should also illustrate
multiple regions of involvement and one irregular node should be
excised for biopsy. First line treatment for HHV-8 positive, MCD is
rituximab (anti-CD 20 antibody) and ganciclovir. With only ten
patients in the literature identified as HIV negative, HHV-8
positive MCD, seven have died, many within several months after
diagnosis. This case highlights the importance of a team-based
approach in evaluating complex FUO cases where the internist plays
a key role not only as a great diagnostician but also as a leader
and care coordinator.
October 2015 Issue of IMpact