Case Presentation: A 32-year-old woman with no medical history presented to the hospital with 10 weeks of fevers, night sweats and progressive shortness of breath. Her symptoms began 1 week after her second dose of the Pfizer-BioNtech Covid-19 Vaccine. On admission, the patient was hemodynamically stable and febrile to 104.1. Exam was significant for conjunctival pallor and decreased bibasilar breath sounds. Labs were notable for anemia, leukocytosis, and significantly elevated ferritin and triglycerides. (Refer to table 1 for all lab values). CT of the chest revealed bilateral ground glass opacities concerning for pulmonary edema with associated pleural effusions. Lymph node biopsy was negative for malignancy. Infectious and Rheumatologic workups were negative (Refer to table 2). Given the patient’s elevated ferritin and triglycerides as well as her negative workup, there was a high suspicion for hemophagocytic lymphohistiocytosis (HLH). H score predicted 93-96% probability. Bone marrow biopsy was performed, but given clinical deterioration, the patient was treated empirically with the HLH-94 protocol–dexamethasone and etoposide. Her soluble IL2 receptor was very elevated (14130.2 pg/ml) and her biopsy showed increased histiocytes with hemophagocytosis. The patient improved initially, but her treatment course was complicated by neutropenia, fevers and increased ferritin. There was concern for infection and a repeat CT scan of the chest/abdomen/pelvis showed perinephric stranding suspicious for pyelonephritis. However, in spite of antibiotics, she deteriorated and her case was deemed refractory HLH. She was started on higher dose dexamethasone and emapalumab. After treatment, the patient had marked improvement and was discharged.
Discussion: HLH is a life-threatening condition characterized by a dysregulated hyperinflammatory state secondary to excessive macrophage and T-cell activation. The chronological proximity of the Pfizer covid-19 vaccination and otherwise benign workup, makes the vaccine a potential trigger for this condition in our patient. HLH should be considered in patients presenting with cytopenias, hyperferritemia and unrelenting fevers. Cases of HLH have been identified after administration of the first dose of the AstraZeneca vaccine. The onset of symptoms in these patients was 5 to 8 days post vaccination. Early recognition of HLH based on clinical and serologic findings, along with the knowledge that the COVID vaccine can cause an inflammatory response such as this, is crucial in hospital medicine to ensure prompt treatment as HLH is universally fatal if untreated.
Conclusions: The covid-19 pandemic has caused millions of deaths worldwide and continues to be a public health threat. Overall, vaccines remain safe and effective. It is essential to continue our ongoing efforts to educate and vaccinate the public. As with all vaccines, there is potential for adverse effects and hospitalists must be cognizant of the possible consequences as we continue to be at the forefront of the pandemic. This case demonstrates HLH as a rare and potentially fatal condition that may result from administration of the Pfizer-BioNtech covid-19 vaccine. It is important to have a high clinical suspicion for the diagnosis of HLH in a patient exhibiting signs and symptoms of HLH after getting the covid-19 vaccine without another identifiable cause. Early initiation of treatment can decrease mortality and improve outcomes.
