Ehrlichiosis-Associated Hemophagocytic Lymphohistiocytosis: A Case Series and Review of the Literature

Table 1

Characteristics of patients with Ehrlichia-associated HLH.

Study	Pt #	Sex	Age	HLH-2004 criteria	Immunosuppression	Treatment	Complications	Outcome
Hammoud et al.	1	F	4	Fever, splenomegaly, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg	None	Doxy; Dexa	None	Survived
Hammoud et al.	2	F	67	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, splenomegaly	Autoimmune hepatitis-azathioprine	Doxy; Dexa	Relapse of severe thrombocytopenia responded to another course of doxy	Survived
Hammoud et al.	3	M	47	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph, low, splenomegaly, ↑TG	None	Doxy; Dexa; HLH-94; Rituximab	Meningoencephalitis hemodiaysis respiratory failure	Survived
Hammoud et al.	4	F	69	Fever, cytopenia, ↓Fbg, ↑ferritin, ↑sIL2R, BM hemoph, ↑TG	Alcoholism	Doxy, HLH-94	Seizure, myocarditis, severe AKI	Survived
Agudela Higata et al. [6]	5	M	49	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph, low NK, splenomegaly	Psoriatic arthritis; -methotrexate; -sulfasalazine	Doxy	Bipolaris fungal pneumonia	Survived
Agudela Higata et al.	6	F	62	Fever, cytopenias, ↑ferritin, ↑sIL2R, ↓ BM hemoph	None	Doxy; HLH-94	Respiratory failure	Survived
Cheng et al. [7]	7	M	9	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph	None	Doxy; HLH-94	Multiorgan failure ECMO	Survived
Dahm et al. [8]	8	M	41	Fever, cytopenia, ↑ferritin, ↑sIL2R, low NK	None	Doxy	Myocarditis	Survived
Dahm et al.	9	F	60	Fever, ↑ferritin, ↑sIL2R, ↓Fbg, low NK, ↑TG	None	Doxy	Myocarditis and acute CHF	Died
Dahm et al.	10	M	68	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph, low NK	None	Doxy; Dexa	Myocarditis, VT, acute CHF, multiorgan failure	Died
Otrock et al. [9]	11	F	52	Fever, cytopenia, ↑ferritin, ↑sIL2R, BM hemoph, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	12	F	47	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	13	F	59	Fever, cytopenia, ↑ferritin, BM hemoph, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	14	F	16	Fever, cytopenia, ↑ferritin, BM hemoph, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	15	M	62	Fever, cytopenia, ↑ferritin, splenomegaly, ↑TG	Bilateral lung transplants	N/A	N/A	Survived
Otrock et al.	16	F	9	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph, low NK, ↑TG	N/A	Doxy; HLH-94	Recurrent Ehrlichia and HLH	Survived
Otrock et al.	17	F	7	Fever, cytopenia, ↑ferritin, ↑sIL2R, splenomegaly, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	18	M	77	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↑TG	N/A	N/A	Septic shock	Died
Otrock et al.	19	M	11	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↑TG	N/A	N/A	N/A	Survived
Otrock et al.	20	F	7	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg	N/A	N/A	N/A	Survived
Cabler et al. [10]	21	F	8	Fever, cytopenia, ↑ferritin, ↓Fbg, BM hemoph, splenomegaly, ↑TG	None	Doxy	None	Survived
Cabler et al.	22	F	3	Fever, cytopenia, ↑ferritin, ↓Fbg, BM hemoph, low NK, splenomegaly, ↑TG	None	Doxy, HLH-94, IT MTX, HCT	AKI, hemorrhagic cystitis, CMV viremia	Survived
Cabler et al.	23	F	7	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, splenomegaly, ↑TG	None	Doxy, HLH-94	Shock, multisystem organ failure	Died
Cabler et al.	24	F	1.3	Fever, cytopenia, ↑ferritin, low NK, splenomegaly	None	Doxy	Seizure Ehrlichia meningitis	Survived
Cabler et al.	25	M	6	Fever, cytopenia, ↑ferritin, ↓Fbg, BM hemoph, ↑TG	None	Doxy; Dexa	Shock	Survived
Cabler et al.	26	F	5	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, ↑TG	None	Doxy	Shock, resp failure, AKI, seizures	Survived
Cabler et al.	27	M	4	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, ↑TG	None	Doxy	Shock, resp failure, AKI, encephalopathy	Survived
Cabler et al.	28	F	6	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↓Fbg, BM hemoph, low NK, splenomegaly, ↑TG	None	Doxy, HLH-94	PRES, relapsed Ehrlichia	Survived
Mitma et al. [11]	29	M	72	Fever, cytopenia, ↑ferritin, ↑sIL2R, ↑TG	MM, HCT	Doxy, MP, tocilizumab	Refractory shock	Died
Kumar et al. [12]	30	M	63	Fever, cytopenia, ↑ferritin, ↓Fbg, splenomegaly, ↑TG	Renal transplant	Doxy, anakinra, MP	None	Survived
Patel et al. [13]	31	M	63	Fever, cytopenia, ↑ferritin, ↑sIL2R, splenomegaly, ↑TG	None	Doxy	Resp failure	Survived
Naqash et al. [14]	32	F	66	Fever, cytopenia, ↑ferritin, ↓Fbg, BM hemoph, low NK, ↑TG	HIV	Etoposide, dexa	Multiorgan failure	Died
Badireddy et al. [15]	33	M	74	Fever, cytopenia, ↑ferritin, BM hemoph, ↑TG	None	Doxy	None	Survived
Kaplan et al. [16]	34	F	41	Fever, cytopenia, ↑ferritin, ↓Fbg, BM hemoph, low NK, ↑TG	None	Prednisone, IVIG, doxy	AKI, meningitis	Survived

Abbreviations. F: female; M: male; sIL2-R: soluble Interleukin-2 receptor; Fbg: fibrinogen; TG: triglyceride; BM hemoph: bone marrow hemophagocytosis; NK: natural killer cell activity; N/A: not available; Doxy: doxycycline; Dexa: dexamethasone; IT MTX: intrathecal methotrexate; AKI: acute kidney injury; HCT: hematopoietic stem cell transplant; resp: respiratory; VT: ventricular tachycardia; CHF: congestive heart failure; PRES: posterior reversible encephalopathy syndrome; MM: multiple myeloma; MP: methylprednisolone; ECMO: extracorporeal membrane oxygenation; RA: rheumatoid arthritis; IVIG: intravenous immunoglobulin.