PGY3 Katharine Yang presented a case of a 68 y/o F with history of DM Type 2, HTN, HLD, hypothyroidism and skin cancer of nose s/p resection and radiation in 2019 presents with altered mental status x 2 weeks and suprapubic pain x1 week. Per son, 5 days prior to presentation, the patient also reported generalized body aches, fatigue and 5 pound unintentional weight loss. Medications include metformin, glipizide, levothyroxine, benazepril and simvastatin. Denies tobacco/ethanol/drug use. Patient is from Mexico, no recent travels.
Vitals: T 39.5, HR 105, RR 24, BP 175/67, O2 sat 97% RA
Physical Exam significant for alert and oriented x0-3 depending on the day, speaking with effort in short phrases, normal cardiac and pulmonary exam, no tenderness to the abdomen and neuro exam non-focal.
CBC: WBC 26.7> Hb 9.6/Hct 28.7 <Plt 267 (MCV 84, RDW 15.8%)
Diff: 83.2% PMN, 7.4% lymph, 9.2% monocytes, 0.1% eosinophils, and 0.1% basophils
Na 130/K 4.7/Cl 98/HCO3 19/BUN 11/Cr 1.16 <Glucose 287
ALP 209>T.protein 6.2/Albumin 3/AST 69/ALT 37/Tbili 0.7/Dbili 0.2
Coags: PT 16.5, INR 1.34, PTT 37.3
TSH 2.02 (normal 0.27-4.20)
CT Head: no acute intracranial hemorrhage or mass effect.
- BCx negative
- UA negative
- UCx negative
- Procal: 5.01 ng/mL
- COVID-19 not detected
- Lactate: 1.7
- RPR non-reactive
- HIV non-reactive
- CSF Studies:
- Nucleated cells: 1/mm^3
- Lymphocytes: rare
- Monocytes/histiocytes: rare
- RBC 2
- Protein 23
- Glucose 82
- CSF Crypto Ag negative
- CSF Gram stain/culture negative
- Meningitis/Encephalitis panel not detected
- BAL: predominantly monocytes/histioytes, rare small lymphocytes observed, no malignant cells identified
- Peripheral smear: leukemoid reaction with a few immunoblasts
- Iron panel:
- Iron 27 mcg/dL
- TIBC 202 mcg/dL
- Iron Sat 13%
- Ferritin 3144 ng/mL
- IL 2R 41,719 (high)
- TG 387 (high)
- LDH 925 U/L (normal 135-225)
- Haptoglobin 238 mg/dL (normal 30-200)
- Fibrinogen 494 mg/dL (normal 237-481)
- DDimer 3.6 mcg/mL (normal <0.49)
CT Thorax/Abdomen/Pelvis showed multiple bilateral peripheral and subpleural pulmonary nodules, multiple mediastinal and hilar lymphadenopathy including a 12mm R paratracheal lymph node, a 10mm subcarinal lymph node, and hepatomegaly.
Bone marrow biopsy performed with confirmation of CD-5+ diffuse large B cell lymphoma, non-germinal center B cell subtype.
Treatment: Patient was transferred to Heme wards after bone marrow biopsy results and she was started on REPOCH given concern for HLH and thus etoposide was included in her chemo regimen.
Take home points:
- Hemophagocytic Lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by an ineffective and hyperactive immune response of T cell lymphocytes and macrophages.
- Hyper-activation of CD8+ T lymphocytes and macrophages
- Proliferation, ectopic migration and infiltration of these cells into organs
- Cytokine storm leading to organ failure and possible death
- Types of HLH: Genetics vs Acquired (infections, malignancy primarily NK/T cell and B cell lymphomas, autoimmune conditions and other – post transplantation, pregnancy, drug induced)
- Presentation: fever, hepatosplenomegaly, bleeding, skin rash, CNS abnormalities, jaundice and lab abnormalities (cytopenias, coagulopathy, hyperlipidemia, hypofibrinogenemia, hyperferritinemia, transaminitis, hyperbilirubinemia, hypoalbuminemia, hyponatremia)
- Diagnosis based on criteria of HLH-2004 diagnostic criteria or H-score
- Treatment: immunosuppressive therapy (dexamethasone, cyclosporine), etoposide, intrathecal MTX in patients with CNS-HLH that did not remit after 2 weeks of dexamethasone. Additionally, the patient should be treated for the underlying cause as well.