Reactive Hemophagocytic syndrome (RHS) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow (BM) and other tissues. It can present in association with infectious etiologies, malignancies, genetic or autoimmune disorders. We report a case of a 36 year old Caucasian gentleman who presented to us with evolving rashes, fever, splenomegaly, mediastinal lymphadenopathy. The diagnosis was made complicated by similar but less severe presentation in other soldiers at the airbase.
A 36-year-old man, on active duty outside US, developed a trunk sparing salmon colored rash with fever, generalized mayalgia, and high grade fever and was sent back to the US for evaluation. Off note, the patient had 7–8 similar episodes over 18 months prior to referral to our institution. The investigations for autoimmune and infectious causes prior to the referral were largely inconclusive. The patient’s condition deteriorated rapidly within 24 hours of admission to require respiratory and circulatory support, and renal replacement. He was presumptively treated for infectious etiology with broad spectrum antibiotics, antifungal, anti parasitic and antiviral medications. The patients location and occupation and the presumptive exposures to exotic zoonotic disorders and toxins, made the differential quite large. Infectious panel sent with guidance from CDC were all negative. The striking positive lab result was very high Ferritin levels. Ferritin levels were repeatedly sent along with panel to evaluate for rheumatologic/autoimmune diseases. Patient’s complete blood count (CBC) demonstrated evolving neutropenia, anemia(figure 1) and thrombocytopenia. Further investigation of the anemia demonstrated hemophagocytosis in blood and marrow with granulocytic/megakaryocytic hyperplasia (figure 2). Adult Onset Still’s Disease (AOSD) was considered as the likely cause of the hyper-immune response on clinical basis due to high grade intermittent fevers, high ESR, splenomegaly and lack of investigative support for malignancy, infectious or another autoimmune cause. Patient was placed on high dose steroids and decision was made to place him on daily Intravenous Immunoglobulin (IVIG) to modulate the hyperimmune response to the inciting factor. After the institution of the IVIG the ferretin level peaked at 3700 ng/ml and then trended to more normal levels of 100ng/ml. The patient’s general condition also demonstrated slow progress to stabilization and finally a transfer out of the Intensive care unit.
RHS is a rare complication of AOSD. It might be more prevalent than we realize due to lack of routine evaluation in stable AOSD patients. The symptoms may include high grade fever, evanescent rashes, jaundice, myalgias, mild hepato-splenomegaly and can also at times lead to systemic inflammatory response syndrome (SIRS) with multi-organ failure and DIC. The syndrome is characterized by demonstrable hemophagocytosis in peripheral blood smear and bone marrow smears, pancytopenia, granulocytic and megakaryocytic hyperplasia in the BM, hyperferritinemia, and hypertriglyceridemia.The exact pathology hasn’t been elucidated but reactive macrophages are thought to result in high ferritin levels, interleukins (IL) and tumor necrosis factor α. Most of the treatment strategies recommend immunomodulation with steroids alone or in combination with IVIG, TNF α blockers and cytotoxic chemotherapy.
Hemophagocytic syndrome can be a rare but life threatening complication associated with AOSD and many other conditions. High suspicion is needed to look for this entity in critically ill patients without any clear etiology of multiorgan failure. Blood and marrow exam is diagnostic. Immune modulating therapies like IVIG, steroids and TNF blockers may have a role to play in reversing the hyper immune response and should be considered early as life saving therapy.
Nikhil Meena, No Financial Disclosure Information; No Product/Research Disclosure Information