Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study

* INCLUSION CRITERIA: * Aged 18 years or older. * Established diagnosis of sHLH defined by meeting any published criteria, per Table 1: * Meeting the HLH-2004 criteria. * HScore of \>168. For those without a bone marrow biopsy to evaluate for hemophagocytosis (worth 35 points in the criteria), HScore\>134 will be used. * For those with underlying rheumatologic disease: meeting the 2016 American College of Rheumatology criteria for macrophage activation syndrome. * Agree to storage and sharing of study data and biospecimens for future research use. Table 1: Published Criteria for HLH HLH-2004 Criteria: Molecular diagnosis of HLH OR At least 5 of 8 below criteria: * Fever (\>38.4 Degrees Celcius) * Splenomegaly * Cytopenias affecting \>=2 of 3 lineages: Hgb \<9 g/dL, platelets \<10\^5/microliter, neutrophils \<10\^6/microliter * Hypertriglyceridemia (\>256 mg/dL) and/or fibrinogen \<1.5 g/L * Hemophagocytosis on biopsy * Serum ferritin \>=500 ng/mL * Increased serum sCD25 (\>2400 U/mL) * Low or absent NK cell activity HScore: Known immunosuppression: 0 (no) or 18 (yes) Temperature (degrees, Celsius): 0 (\<38.4), 33 (38.4-39.4), 49 (\>39.4) Organomegaly: 0 (no), 23 (liver/spleen), 38 (both) Number of cytopenias: 0 (1 lines), 24 (2 lines), 34 (3 lines) Ferritin (ng/mL): 0 (\<2000), 35 (2000-6000), 50 (\>6000) Triglycerides (mg/dL): 0 (\<1.5), 44 (1.5-4), 66 (\>4) Fibrinogen (g/L): 0 (\>2.5), 30 (\<2.5) AST (IU/mL): 0 (\<30), 19 (\>30) Hemophagocytosis: 0 (no) or 35 (yes) Cutoff value=169 ACR 2016-MAS Criteria: A febrile patient with known or suspected sJIA is classified as having macrophage activation syndrome if the following criteria are met: Ferritin \>684 ng/mL AND any 2 of the following: * Platelets \<=181,000/microliter * AST \>48 IU/mL * Triglycerides \>156 mg/dL * Fibrinogen \<=3.6 g/L Abbreviations: ACR, American College of Rheumatology; AST, aspartate transaminase; Hgb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; MAS, macrophage activation syndrome; NK, natural killer, sJIA, systemic juvenile idiopathic arthritis. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Currently pregnant. * Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.