Case Presentation: A 50-year-old Hispanic female with a history of obsessive-compulsive disorder and anemia presented to the emergency department with complaints of dyspnea after a syncopal episode. Patient also noted a 30 pound weight loss and non-healing wound ulcers of all four extremities over 3 months. On presentation, patient’s vitals were notable for BP=105/65, HR=120, RR=22, temperature=103.0 F, and a BMI=15 kg/m2. Physical examination demonstrated a cachectic appearing female with scattered non-purulent gangrenous lesions in all four extremities and diminished right-sided breath sounds. Labs showed WBC=11.5 with normal differential, Hgb=8.6, Hct= 27.2, MCV=72.0, platelet=54, AST=112, ALT=76, and Bilirubin=2.6. Iron studies, ANA, HIV, and hepatitis panel were unremarkable. She required intubation and chest tube placement due to impending respiratory failure from a right-sided hemopneumothorax. Her condition worsened despite receiving intravenous antibiotics for sepsis secondary to pneumonia and infected non-healing wounds growing Pseudomonas aeruginosa. Patient was treated for sepsis approximately 10 days without improvement and another diagnosis needed to be considered. Given the history of cachexia and other subtle clues, our team was concerned for possible underlying hematologic pathologies such as hemophagocytic lymphohistiocytosis (HLH) which prompted ordering of triglyceride and ferritin level. The combination of elevated triglyceride=419, ferritin=4880, bi-lineage cytopenia, splenomegaly on imaging, and fever confirmed 5/8 of the HLH-2004 diagnostic criteria and patient was subsequently started on high dose IV dexamethasone. A punch biopsy of skin lesions revealed extranodal NK/T-cell lymphoma, nasal type (ENKL) but patient was deemed a poor candidate for chemotherapy. After three days of IV dexamethasone therapy, patient’s clinical status continued to worsen, and she expired from respiratory failure.
Discussion: HLH is a severe hyperinflammatory syndrome induced by aberrantly activated cytotoxic T cell/macrophages which leads to disruption of immune homeostasis manifesting as recurrent fever, liver dysfunction, cytopenia, and a sepsis-like syndrome. Prompt treatment is critical, but the challenge to successful outcome is delay in diagnosis due to rarity of syndrome and variable clinical presentation. In our patient, what was thought to be a non-resolving sepsis was in fact a hyperinflammatory response to ENKL as HLH occurs in 3 percent of all cases. Perhaps the sepsis was the inciting event of the HLH but in our case malignancy could have led to this patient’s demise even before arrival to the hospital.
Conclusions: This case illustrates the importance of cognitive biases such as confirmation bias and availability heuristic which could have led to a delay in diagnosis and management. Albeit, HLH is far less common, clinicians should be aware because early recognition may prevent irreversible organ damage and death much like sepsis. Additionally, special attention should be made in the HLH adult population as malignancy is often a trigger for this sepsis-like syndrome.