A 66-year-old man presents with a one-year history of pancytopenia, periodic fevers, rigors, and the appearance of erythematous nonpruritic sloughing papules on his arms and legs. He was admitted to the hospital because of the development of orthostatic hypotension.
Physical examination revealed a temperature of 36.6°C, a pulse rate of 91 beats per minute, a blood pressure of 119/71 mmHg (75/48 while standing), and a respiratory rate of 16 breaths per minute. The examination was positive for pallor, marked edema of the legs and periorbital region, scattered mummular and erosive lesions with overlying eschars on both feet, both forearms, and right thigh and petechiae on the arms and chest.
Pertinent laboratory findings included pancytopenia and hyperferritinemia (12,620 ng/mL) with a normal serum iron, transferrin saturation, and diminished total iron-binding capacity. The results of a bone marrow biopsy and aspirate are shown in the panel below. What is your diagnosis, what test(s) would you order to confirm your suspicions, and what treatment, if any, do you recommend?
Hematoxylin and esosin staining of a marrow biopsy (Panel A) and Giemsa staining of aspirate (Panels B, C) show numerous histiocytes with engulfed erythroid elements (Panel B) and mature erythrocytes (Panel C). Immunohistochemical staining for CD163 shows histiocytes filled with intracytoplamic erythrocytes. Dashed lines outline hemophagocytic histiocytes.
DIAGNOSIS: Reactive hematophagocytic syndrome (RHS) in association with lymphoma.
RHS is an uncommon potentially fatal syndrome caused by the widespred non-neoplastic proliferation and inappropriate activation of immature macrophages, resulting in excessive cytokine activation which leads to hematophagocytosis by cells of the monocyte-macrophage lineage and multiorgan dysfunction. RHS may be associated with infections (viral, bacterial, fungal), lymphoproliferative disorders, nonhematopoietic malignancies and autoimmune diseases. This patient's laboratory findings are characteristic of the disorder. Treatment consists of corticosteroids plus treatment of the underlying (triggering) disorder.