First Author: Nikhil A. Patel, Mayo Medical School, Class of 2015
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 disease.
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.