Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

doi:10.1007/s11684-013-0292-0

Frontiers of Medicine

2013, Vol. 7

Issue (4): 492-498 https://doi.org/10.1007/s11684-013-0292-0

RESEARCH ARTICLE

本期目录

Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition

Somanath Padhi¹(

), Renu G’ Boy Varghese¹, Anita Ramdas¹, Manjiri Dilip Phansalkar¹, RajLaxmi Sarangi²

1. Department of Pathology, Pondicherry Institute of Medical Sciences, Ganapathichettykulam, Kalapet, Puducherry 605 014, India; 2. Department of Biochemistry, Pondicherry Institute of Medical Sciences, Ganapathichettykulam, Kalapet, Puducherry 605 014, India

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Abstract：

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs include prolonged fever, organomegaly, and persistent unexplained cytopenias. In spite of the well known diagnostic criteria put forth by HLH society, this continues to pose great diagnostic challenge in both pediatric and adult intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29, 40, and 17 years) and 3 pediatric (2 males, 1female, aged 1 month, 6 months, and 12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic criteria. Definite evidence of hemophagocytosis was noted in 4 patients on initial bone marrow examination. The underlying etiologies were as follows: Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was presumed to have been exacerbated by administration of granulocyte monocyte colony stimulating factor (GM-CSF) for severe neutropenia. Two patients died with disseminated intravascular coagulation (DIC) and multi organ failure within few days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and etoposide was started in one patient only. Due to lack of specificity of diagnostic criteria, diagnosing and differentiating HLH from its closest mimickers like sepsis/septic shock may be quite challenging in critically ill patients. Therefore, increasing awareness among physicians is essential for early diagnosis and effective therapy to reduce the mortality.

Key words： hemophagocytic lymphohistiocytosis diagnosis therapy GM-CSF bone marrow

收稿日期: 2013-05-09 出版日期: 2013-12-05

Corresponding Author(s): Padhi Somanath,Email:somanath.padhi@gmail.com

引用本文:

. Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition[J]. Frontiers of Medicine, 2013, 7(4): 492-498.
Somanath Padhi, Renu G’ Boy Varghese, Anita Ramdas, Manjiri Dilip Phansalkar, RajLaxmi Sarangi. Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition. Front Med, 2013, 7(4): 492-498.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-013-0292-0
https://academic.hep.com.cn/fmd/CN/Y2013/V7/I4/492

Patient characteristics	Case 1	Case 2+	Case 3	Case 4	Case 5	Case 6	Case 7
Age (years)/gender	19, female	29, female	12, male	40, male	1, male	6/12, female	17, male
Managing departments	ICU^(a)	ICU	Orthopaedics	ICU	ICU	ICU	ICU
Presumptive diagnosis	?Sepsis	?Sepsis	sJIA^(b)/leukemia/ tuberculosis	?Sepsis/SIRS^(c)	?HLH	?Storage disorder	?Sepsis, atypical pneumonia
HLH-2004 criteria
Fever	+^(d) (3 weeks)	+ (3weeks)	+ (6 months)	+ (2 weeks)	+ (1 week)	+ (2 weeks)	+ (2 months)
Splenomegaly±hepatomegaly	+	+	+	+	+	+	+
Cytopenia (≥2 cell lines)	+	+	+	+	+	+	+
? Hemoglobin≤90 g/L	+ (66 g/L)	+ (90 g/L)	+ (88 g/L)	+ (66 g/L)	+ (90 g/L)	+ (39 g/L)	+ (68 g/L)
? Platelet count≤100×10⁹/L	+ (80×10⁹/L)	+ (30×10⁹/L)	–^(e)	+ (40×10⁹/L)	+ (90×10⁹/L)	+ (68 x10⁹/L)	-
? Absolute neutrophil count (<1000/L)	+ (675/L)	-	+ (688/L)	+ (160/L)	-	-	+ (792/L)
Fasting serum triglyceride (>265 mg/dl)	760	503	-	Not done	277	660	-
Hypofibrinogenemia (<150 mg/L)	-	+	-	+	-	Not done	+ (>2000)
Hyperferritinemia (>500 μg/L)	+ (>30,000)	+ (>2000)	589	+ (>1000)	793	840	-
Hemophagocytosis in bone marrow	+	+ (marked)	+	+	not evident^(f)	(g)	Not evident
Natural Killer cell activity ^(h)	Not done	Not done	Not done	Not done	Not done	Not done	Not done
Soluble CD25⁽ⁱ⁾	Not done	Not done	Not done	Not done	Not done	Not done	Not done
Molecular testing^(j)	Not done	Not done	Not done	Not done	Not done	Not done	Not done
Supportive laboratory features^(k)
Liver transaminases (≥200IU/L)	+	+ (>1000)	-	+	-	-	-
Hyperbilirubinemia (mg/dl) (T/D)	1.285714286	1.607142857	-	1.428571429	-	-	-
Prolonged PT±aPTT	+	+	-	+	-	-	+
Lactate dehydrogenase (IU/L)	3000	Not done	267	889	Not done	Not done	903
Hypoalbuminemia (<3.5 g/dl)	2.5	2.2	-	2.8	-	-	2.2
Hyponatremia (<135 meq/L)	126	125	-	128	-	-	125
D-dimer (semi-quantitative)	-	800	-	+	-	Not done	-
Antinuclear antibody	-	+	-	-	-	Not done	-
Procalcitonin (ng/dl)	+ (>100)	+ (>100)	Not done	+ (>100)	Not done	Not done	+ (>100)
Etiology screen	Rickettsia tsutsugamushi (IgG ELISA) and secondary bacterial infection	Autoimmune ds with sepsis (MAS)^(l)	sJIA (MAS) HLA-B27 & IgM rheumatoid factor negative	? Viper snake bite, SIRS, GM-CSF^(m) aggravated	Plasmodium vivax (card test+)	CMV⁽ⁿ⁾ (IgG ELISA+)	Miliary TB^(o) and bone marrow caseating granulomas
Management	IV antibiotics, doxycyclin, ventilator support, vasopressor, steroids, etoposide	IV antibiotics, vasopressor, steroids, ventilator support, FFP^(p)	IV antibiotic+ tablet naproxen (10 mg/ kg) + low dose steroid	IV antibiotics, vasopressor, steroids, ventilator support, FFP	Syrup chloroquine+ primaquine+ IV antibiotic	Supportive care+ IV antibiotics	Ventilator support+ IV antibiotic+ ATT^(q)
Outcome	Alive, on follow-up	DIC^(r), MOF^(s), death	Alive, on follow-up	DIC, MOF, death	Alive	Alive, on follow-up	On follow-up

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