Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
Background: Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by disrupted immune function. People with HLH are prone to fevers and illnesses, which can be fatal. Some people develop a genetic form of this disease (pHLH), but researchers do not understand why some other people develop a nongenetic form (sHLH). They also do not have good ways to diagnose and treat sHLH.
Objective: To learn about sHLH and why some people get it and others do not.
Eligibility: Adults aged 18 years and older with sHLH.
Design: Participants will be admitted to the study based on a review of their medical records. Those who join will have at least 3 clinical evaluations over 9 to 12 months. These may occur during an inpatient hospitalization if they require medical care or in the outpatient clinic. Participants will also have a physical exam at each visit. Up to half a cup of blood will be drawn at each visit. Participants may also have their blood drawn by their own doctors, who will send the samples to the researchers. Researchers may also contact these participants by telephone or video calls. The blood will be used for clinical tests as well as research. No new treatments will be administered as part of this study; however, standard medications and treatments may be recommended. Participants may opt to continue their visits once a year for 3 more years. Participants may also opt for an extra clinial evaluation 1 week after starting a new treatment....
• 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.