This is a 22–year–old female with history of SCD and MAC, diagnosed one month prior, who presented with complaints of shortness of breath, pain in lower back and legs, nausea and vomiting. Chest x–ray showed patchy infiltrates in both lungs. She was admitted for sickle cell crisis with acute chest syndrome. IV antibiotics for treatment of bacterial pneumonia and MAC were initiated, along with blood transfusion, fluid resuscitation and oxygen [O2] support for sickle cell crisis. Course was complicated by high fevers and hepatitis with cholestatic pattern. Cultures were negative. Ultrasound and CT abdomen without evidence of biliary dilatation; gallbladder was surgically absent. With time, O2 requirements increased, along with worsening conjugated bilirubinemia. Exchange transfusion was contemplated but her hemoglobin S was >30%, therefore precluding the benefit of this therapy. Respiratory failure and coagulopathy with low fibrinogen ensued. An extremely elevated ferritin level of 38,539 ng/ml and elevated triglycerides were noted. All these features raised the suspicion for HLH syndrome. Bone marrow biopsy showed evidence of hemophagocytosis. Diagnosis of HLH was confirmed as she met diagnostic criteria. Solumedrol 1g IV daily and Anakinra 100 mg SC daily was started. Etoposde was not given due to her liver dysfunction. Despite dramatic improvements in her overall condition, her respiratory status continued to deteriorate. Patient made herself DNR. She was transferred to the palliative medicine service. She expired due to respiratory arrest.
HLH is characterized by uncontrolled activation and proliferation of macrophages with a marked increase in circulating cytokines. It has been linked to specific genetic abnormalities in children (primary HLH) and occurs sporadically in adults secondary to the presence of another condition such as viral illness, autoimmune disease, or lymphoma (secondary HLH). Diagnostic criteria includes fever; hyperferritinemia >500 microg/L; splenomegaly; cytopenia; hypofibrinogenemia, hypertriglyceridemia; hemophagocytosis in bone marrow, spleen, or lymph nodes; natural killer cell activity low or absent and soluble interleukin–2 receptor = 2400 U/ml. Diagnosis relies on meeting five of the eight findings as outlined above. HLH mortality is very high, up to 95%, depending on the underlying cause. Most commonly used treatment includes a combination of high–dose glucocorticoids, etoposide and methotrexate. Other treatments are interleukin–1 receptor antagonists, cyclosporine and IVIG.
Incidence of HLH is unknown. To our knowledge there are no reported cases of HLH in patients with SCD or mycobacterium infection. Hospitalists should be aware of this rare condition and it should be in the differential diagnosis in patients with persistent fevers, cytopenias and extremely high ferritin levels.