A 49 year old man with AIDS on anti-retroviral therapy (CD4 count 113) presented to the hospital with dizziness, abdominal pain, and generalized fatigue and malaise. He developed fever as high as 39.9 degree Celsius shortly after admission along with anemia and thrombocytopenia. The patient underwent complete infectious workup including viral and atypical panels given his low CD4 count. All of these resulted negative. He developed tender and enlarged cervical and supraclavicular lymph nodes as well as enlarged axillary and inguinal lymph nodes. Computed tomographic (CT) scan of the chest, abdomen and pelvis with the administration of intravenous contrast demonstrated hilar and mediastinal lymphadenopathy in the chest along with diffuse lymphadenopathy throughout the abdomen and pelvis; there was hepatosplenomegaly. The patient underwent excisional biopsy of a supraclavicular lymph node and because he had home exposure to cats, serological testing was conducted which resulted with positive IgG to Bartonella quintana at a titer of 1:512. He was started on doxycycline for treatment of bacillary angiomatosis. Pathology revealed atypical interfollicular plasmacytosis with focal lamda light chain- restricted immunoblasts and HHV8 positive cells, consistent with multicentric Castleman disease and the patient was referred to a tertiary care HIV clinic and oncology for follow-up and treatment, with plan to start rituximab and chemotherapy.
Discussion:
Castleman disease is a rare lymphoproliferative disease associated with infection of HIV and HHV-8. It is also associated with other malignancies such as lymphoma and Kaposi’s sarcoma, as well as POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes). It can be characterized as either unicentric or multicentric, with the latter portending a worse prognosis. Patients often present with non-specific symptoms, such as our patient here, and the diagnosis is often delayed while patients are evaluated for more common etiologies. Definitive diagnosis requires biopsy and treatment varies depending on HHV-8 positivity. The combination of fever, lymphadenopathy, splenomegaly, and elevated CRP should raise suspicion for the possibility of this diagnosis, though biopsy is required for definitive diagnosis. There are no validated diagnostic criteria to guide in diagnosis of HIV MCD, though Gerard et al.have posited a definition on the experience of the CastlemaB trial group.
There is no established therapy for HIV MCD and relapse is common. Data on treatment is limited but case reports and small prospective non- randomized trials show that rituximab is effective with the addition of etoposide for aggressive disease. Rituximab is associated with worsening of Kaposi’s sarcoma, making treatment more challenging in patients with both disease processes.
Our patient, sadly, succumbed to his disease not long after referral, highlighting the aggressive nature of this condition.
Conclusions:
The clinician must have high index of suscpicion for multi-centric Castleman disease when a patient with HIV/AIDs presents with fever, diffuse lymphadenopathy, splenomegaly and elevated CRP. The diagnosis can easily be missed or delayed while awaiting evaluation for more common etiologies. This disease can be very aggresive and rapidly fatal if missed.