Case Presentation: A 65-year-old female with a history of iron deficiency and acute blood loss anemia, schizophrenia, asthma, and hypothyroidism presented with shortness of breath and weight loss for three months. On arrival, her temperature was 101.1 F, blood pressure 84/40, heart rate 129, and spO2 97% on room air. Laboratory studies showed a white blood cell count (WBC) 8.55 K/uL, hemoglobin (hgb) 6.7 g/dL, platelets 228 K/uL, ferritin 18,677 ng/ml, creatinine 0.60 mg/dL, total bilirubin 0.9 mg/dL, alkaline phosphatase (ALP) 376 U/L, ALT 30 U/L, and AST 40 U/L. Blood cultures were negative. Urinalysis indicated infection, prompting initiation of ceftriaxone. Computed tomography (CT) of the chest revealed enlarged mediastinal, retroperitoneal, and left supraclavicular lymph nodes. A biopsy of a left supraclavicular lymph node confirmed lymphocyte-depleted classical Hodgkin lymphoma (LDCHL). Bone marrow biopsy showed no evidence of lymphoma.Given the patient’s persistent fevers, elevated ferritin, and evidence of liver dysfunction, there was concern for hemophagocytic lymphohistiocytosis (HLH). Additional laboratory studies revealed WBC 7.64 K/uL, hgb 8.1g/dL, plt 94 K/uL, triglycerides 282, fibrinogen 628, ferritin 25,218, and soluble IL-2 receptor (sIL-2) level 8128, corresponding to an H score of 187. Dexamethasone per HLH-2004 protocol was started; however, the patient subsequently developed respiratory failure and shock requiring intubation and pressor support. Repeat CT chest showed severe lymphadenopathy compressing the trachea. She was deemed too unstable to begin chemotherapy. Per family wishes, medical care was withdrawn, and the patient was compassionately extubated.
Discussion: HLH is a rare, life-threatening hyper-inflammatory disorder characterized by excessive immune activation, leading to multi-organ failure. Diagnosis is confirmed with five of eight criteria: fever, splenomegaly, cytopenia, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, low or absent natural killer cell (NK) activity, ferritin ≥500 ug/L, and sIL-2 ≥2400 U/mL. Among these, elevated ferritin and sIL-2 are particularly specific for HLH. A diagnostic scoring system (H score) utilizes clinical, laboratory, and histopathological factors to estimate the probability of HLH. An increased H score correlates with an increased probability of disease, with a cutoff of 169 and specificity of 86%. HLH can be triggered by underlying malignancy, particularly lymphoma, so it is critical that all HLH patients undergo evaluation for underlying malignancy. LDCHL is an aggressive form of Hodgkin lymphoma, affecting < 1% of patients with HL in Western countries. Management of malignancy-associated HLH can be challenging as it often involves treatment of both HLH and the underlying malignancy. Prognosis for patients with HLH and LDCHL tends to be poor due to the severity of both conditions; however, a multidisciplinary approach can facilitate early diagnosis and initiation of treatment.
Conclusions: HLH is a rare, hyper-inflammatory condition that can be triggered by underlying malignancy. Diagnosis is established if five of eight criteria are met. All patients with HLH should receive evaluation for underlying malignancy. Early intervention and a multidisciplinary approach to treatment are critical for improving outcomes.