CC: fevers, malaise, mild shortness of breath
ID: 40 yo female with no medical history presents for 1 week of fevers, malaise, and mild shortness of breath. She also notes a 1 year history of intermittent fevers, fatigue, chills, night sweats, weight loss, and LUQ abdominal fullness. On exam, she was noted to be febrile to 39.3 with diffuse lymphadenopathy and splenomegaly. She was found to be pancytopenic on presentation with WBC of 1.3, Hgb of 6.5, and Plt of 79. Further workup revealed a ferritin of 2,757, LDH of 617, and triglycerides of 251. Autoimmune labs were negative and a CT scan demonstrated splenomegaly with multiple enhancing lymph nodes throughout. A bone marrow biopsy demonstrated histiocytes comprising 50% of the bone marrow and the patient was diagnosed with hemophagocytic lymphohistiocytosis.
- To meet the criteria for HLH, the patient must have the right clinical picture and 5 of the following:
- fever > 38.5C
- cytopenias (at least bicytopenia with Hgb < 9, Plt < 100, or ANC < 10000)
- hypertriglyceridemia (fasting trigs > 265) and/or hyperfibrinogenemia (fibrinogen < 150)
- hemophagocytosis in bone marrow, spleen, lymph node, or liver
- low or absent NK cell activity
- ferritin > 500 ng/ML
- elevated soluble CD25
Pearls from morning report:
- To examine for splenomegaly, start palpation in RLQ as the spleen enlarges towards that direction.
- The combination of pancytopenia and constitutional symptoms should lead to workup for infection (viral illness, miliary TB, fungal infections, endocarditis), HLH, hematologic malignancy, or autoimmune disease.
- When ferritin levels are significantly elevated (in the high hundreds to thousands), causes that should come to mind include: Still’s Disease, HLH, disseminated histoplasmosis, hemochromatosis, and liver failure.
- The workup of HLH is not complete after its diagnosis – you must evaluate for underlying precipitants/causes of HLH.
HLH was first described in 1939, but more fully understood in 1952 when two siblings in a family passed away from HLH (and another sibling 6 years later).
Want to read more?
Weinzierl KP, Arber DA. The Differential Diagnosis and Bone Marrow Evaluation of New-Onset Pancytopenia. Am J Clin Pathol. 2013;139:9-29.
Berliner N, Gansner JM, Schrier SL, Rosmarin AG. Approach to the adult with unexplained pancytopenia. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on May 19, 2017)