Secondary Hemophagocytic Lymphohistiocytosis (HLH) From a Brown Recluse Spider Bite

Introduction: Systemic loxoscelism is a rare complication from Loxosceles reclusa (brown recluse spider) envenomation that occurs in children more often than adults. It is often difficult to diagnose and there is currently no standard treatment.  Symptoms can consist of localized skin necrosis, organ dysfunction, hemolysis, systemic inflammation, and possible death. We present a case of systemic loxoscelism that presented with renal failure, hepatotoxicity, DIC, hemolytic anemia, and secondary hemophagocytic lymphohistiocytosis (HLH).

Case Report: Our patient is a previously healthy 10 year old male, who developed the acute onset of malaise, nausea, fever, and a right elbow rash while attending camp in Tennessee. Upon presentation to our emergency department one day after the initiation of symptoms, he was noted to have severe renal dysfunction, liver dysfunction, hemolytic anemia, and thrombocytopenia. His physical exam was significant for fever and small, non-purulent blisters with surrounding erythema in the right antecubital fossa. Further investigation revealed elevation of soluble IL-2 receptor (9204  units/ml), ferritin (>40,000 ng/ml), and triglycerides (762 mg/dl) with hypofibrinogenemia (102 mg/dl). A bone marrow aspirate had moderate hemophagocytic activity present. With continued worsening of his organ dysfunction, he was started on high dose dexamethasone therapy for HLH. After initiation of steroid therapy, his organ dysfunction resolved rapidly and he was able to come off dialysis.  His liver dysfunction also resolved and his inflammatory markers normalized. Investigation of his HLH did not reveal any known disease causing mutations.

 Discussion: The clinical course following brown recluse spider bite can be relatively benign to life threatening with severe organ dysfunction and systemic inflammation. Loxosceles venom contains pro-inflammatory proteins which stimulate the production of interleukin-8, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor all of which have been shown to be elevated in patients with HLH. Secondary HLH can be seen in patients without an underlying genetic cause of the disease and is often triggered by a concurrent medical condition.  Loxosceles envenomation should be considered as a potential cause of secondary HLH.