Int J Clin Pediatr

International Journal of Clinical Pediatrics, ISSN 1927-1255 print, 1927-1263 online, Open Access

Article copyright, the authors; Journal compilation copyright, Int J Clin Pediatr and Elmer Press Inc

Journal website https://www.theijcp.org

Case Report

Volume 13, Number 1, May 2024, pages 26-33

X-Linked Lymphoproliferative Disease Type 2 With Activation of Hemophagocytic Lymphohistiocytosis Secondary to Epstein-Barr Virus Infection

Figure 1. HLH-2004 diagnostic criteria commonly used in HLH diagnosis. HLH: hemophagocytic lymphohistiocytosis; NK: natural killer.

**Table 1.** Significant Investigations Conducted Upon Admission
Investigation	Results^a
^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; Plt: platelet; CRP: C-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; γGTP: γ-glutamyl transpeptidase; PT: prothrombin time; PTT: partial thromboplastin time; ESR: erythrocyte sedimentation rate; G6PD: glucose-6-phosphate dehydrogenase; INR: international normalized ratio.
Blood cultures	No growth
Complete blood count (CBC)
WBC (× 10³/µL)	7.8 (6 - 18)
RBC (× 10⁶/µL)	4.24 (3.5 - 5.2)
Hb (g/dL)	10.1^b (10.5 - 13.5)
Plt (× 10³/µL)	214 (140 - 450)
R-CRP (mg/dL)	2.38^b (0.10 - 0.5)
Procalcitonin	4.87^b (≤ 0.1)
Ferritin (ng/mL)	33,511.20^b (21.81 - 274.66)
Liver function test (LFT)
AST (U/L)	401^b (5 - 34)
ALT (U/L)	141^b (5- 55)
LDH (U/L)	4,709^b (125 - 220)
γGTP (U/L)	127^b (12 - 64)
B12 level (pg/mL)	1,320^b (187 - 883)
PTT (s)	50.2^b (25.6 - 42.3)
Fibrinogen level	122^b (200 - 400)
PT (s)	17.3^b (13.1 - 17.5)
D-dimer	8.16^b (≤ 0.5)
Renal function test (RFT), chest X-ray, venous blood gas (VBG), ESR, hemoglobin electrophoresis, G6PD test, triglycerides, INR, electrolytes, amylase, immunoglobulins, echocardiogram (ECHO), electrocardiogram (ECG), urinalysis and culture, other elements of LFT	Unremarkable

Table 1. Significant Investigations Conducted Upon Admission

Investigation

Results^a

^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; Plt: platelet; CRP: C-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; γGTP: γ-glutamyl transpeptidase; PT: prothrombin time; PTT: partial thromboplastin time; ESR: erythrocyte sedimentation rate; G6PD: glucose-6-phosphate dehydrogenase; INR: international normalized ratio.

Blood cultures

No growth

Complete blood count (CBC)

WBC (× 10³/µL)

7.8 (6 - 18)

RBC (× 10⁶/µL)

4.24 (3.5 - 5.2)

Hb (g/dL)

10.1^b (10.5 - 13.5)

Plt (× 10³/µL)

214 (140 - 450)

R-CRP (mg/dL)

2.38^b (0.10 - 0.5)

Procalcitonin

4.87^b (≤ 0.1)

Ferritin (ng/mL)

33,511.20^b (21.81 - 274.66)

Liver function test (LFT)

AST (U/L)

401^b (5 - 34)

ALT (U/L)

141^b (5- 55)

LDH (U/L)

4,709^b (125 - 220)

γGTP (U/L)

127^b (12 - 64)

B12 level (pg/mL)

1,320^b (187 - 883)

PTT (s)

50.2^b (25.6 - 42.3)

Fibrinogen level

122^b (200 - 400)

PT (s)

17.3^b (13.1 - 17.5)

D-dimer

8.16^b (≤ 0.5)

Renal function test (RFT), chest X-ray, venous blood gas (VBG), ESR, hemoglobin electrophoresis, G6PD test, triglycerides, INR, electrolytes, amylase, immunoglobulins, echocardiogram (ECHO), electrocardiogram (ECG), urinalysis and culture, other elements of LFT

Unremarkable

**Table 2.** Additional Investigations Conducted During the Hospital Admission
Investigation	Results^a
^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. CMV: cytomegalovirus; EBV: Epstein-Barr virus; Ig: immunoglobulin; VCA: viral capsid antigen; EA: early antigen; NA: nuclear antigen; US: ultrasound; COVID-19: coronavirus disease 2019; HIV: human immunodeficiency virus; HSV: herpes simplex virus; PCR: polymerase chain reaction; IL: interleukin.
CMV IgG	Positive^b
CMV IgM	Negative
EBV EA IgG	Positive^b
EBV-M IgM	Positive^b
EBV-NA IgG	Positive^b
EBV-VCA IgG	Positive^b
EBV PCR test	Positive (19,500 copies/mL)^b
Chromosomal analysis	No numerical or structural abnormality detected
Bone marrow biopsy	Normocellular marrow for age with evident hemophagocytosis^b and no evidence of malignancy
Mycoplasma IgG	Negative
Abdomen US	Moderate hepatomegaly with biliary sludge
Rheumatoid factor	< 7
C4 (mg/dL)	22.3 (13 - 57)
Troponin-1 (ng/mL)	< 0.010
Urine protein (mg/dL)	29.3^b (1 - 14)
IgM	188^b (41 - 183)
Rubella IgG	Positive^b
Rubella IgM	Negative
Varicella IgG	Positive^b
Varicella IgM	Negative
COVID-19 IgG	Positive^b
COVID-19 IgM	Negative
COVID-19 PCR	Negative
Hepatitis B and C panel	Negative
HIV panel	Negative
HSV IgG	Positive^b
HSV IgM	Positive^b
IL-1 (pg/mL)	10.2^b (≤ 5.0)
IL-6 (pg/mL)	4.4 (≤ 7.0)

Table 2. Additional Investigations Conducted During the Hospital Admission

Investigation

Results^a

^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. CMV: cytomegalovirus; EBV: Epstein-Barr virus; Ig: immunoglobulin; VCA: viral capsid antigen; EA: early antigen; NA: nuclear antigen; US: ultrasound; COVID-19: coronavirus disease 2019; HIV: human immunodeficiency virus; HSV: herpes simplex virus; PCR: polymerase chain reaction; IL: interleukin.

CMV IgG

Positive^b

CMV IgM

Negative

EBV EA IgG

Positive^b

EBV-M IgM

Positive^b

EBV-NA IgG

Positive^b

EBV-VCA IgG

Positive^b

EBV PCR test

Positive (19,500 copies/mL)^b

Chromosomal analysis

No numerical or structural abnormality detected

Bone marrow biopsy

Normocellular marrow for age with evident hemophagocytosis^b and no evidence of malignancy

Mycoplasma IgG

Negative

Abdomen US

Moderate hepatomegaly with biliary sludge

Rheumatoid factor

< 7

C4 (mg/dL)

22.3 (13 - 57)

Troponin-1 (ng/mL)

< 0.010

Urine protein (mg/dL)

29.3^b (1 - 14)

IgM

188^b (41 - 183)

Rubella IgG

Positive^b

Rubella IgM

Negative

Varicella IgG

Positive^b

Varicella IgM

Negative

COVID-19 IgG

Positive^b

COVID-19 IgM

Negative

COVID-19 PCR

Negative

Hepatitis B and C panel

Negative

HIV panel

Negative

HSV IgG

Positive^b

HSV IgM

Positive^b

IL-1 (pg/mL)

10.2^b (≤ 5.0)

IL-6 (pg/mL)

4.4 (≤ 7.0)

**Table 3.** Trend of CBC, LFT, Triglycerides, Ferritin, and Fibrinogen Levels During Follow-Up Visits
Lab investigations results of each visit^a	First follow-up visit	Second	Third	Fourth	Eighth
^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. CBC: complete blood count; LFT: liver function test; WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; Plt: platelet; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; γGTP: γ-glutamyl transpeptidase.
LFT
AST (U/L) (5 - 34)	29	25	42^b	28	25
ALT (U/L) (5 - 55)	39	50	39	34	12
LDH (U/L) (125 - 220)	440^b	430^b	494^b	429^b	291^b
γGTP (U/L) (12 - 64)	47	35	32	26	11
CBC
WBC (× 10³/µL) (6 - 18)	14.5	16.8	6.0	8.7	10.6
RBC (× 10⁶/µL) (3.5 - 5.2)	4.54	4.62	4.93	4.94	5.11
Hb (g/dL) (10.5 -13.5)	10.6	10.0	10.5	10.1	12.5
Plt (× 10³/µL) (140 - 450)	474^b	-	411	529^b	491^b
Triglycerides (mg/dL) (30 - 200)	90	224^b	106	55	-
Ferritin (ng/mL) (21.81 - 274.66)	13.43	4.93	953.28^b	3.75	44.25
Fibrinogen level (200 - 400)	191	173	623^b	303	-

Table 3. Trend of CBC, LFT, Triglycerides, Ferritin, and Fibrinogen Levels During Follow-Up Visits

Lab investigations results of each visit^a

First follow-up visit

Second

Third

Fourth

Eighth

May 30, 2021

June 6, 2021

June 17, 2021

July 14, 2021

October 12, 2022

^aReference ranges listed above correspond to the reference ranges utilized in our hospital’s laboratory. ^bAbnormal results. CBC: complete blood count; LFT: liver function test; WBC: white blood cell; RBC: red blood cell; Hb: hemoglobin; Plt: platelet; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; γGTP: γ-glutamyl transpeptidase.

LFT

AST (U/L) (5 - 34)

42^b

ALT (U/L) (5 - 55)

LDH (U/L) (125 - 220)

440^b

430^b

494^b

429^b

291^b

γGTP (U/L) (12 - 64)

CBC

WBC (× 10³/µL) (6 - 18)

14.5

16.8

6.0

8.7

10.6

RBC (× 10⁶/µL) (3.5 - 5.2)

4.54

4.62

4.93

4.94

5.11

Hb (g/dL) (10.5 -13.5)

10.6

10.0

10.5

10.1

12.5

Plt (× 10³/µL) (140 - 450)

474^b

411

529^b

491^b

Triglycerides (mg/dL) (30 - 200)

224^b

106

Ferritin (ng/mL) (21.81 - 274.66)

13.43

4.93

953.28^b

3.75

44.25

Fibrinogen level (200 - 400)

191

173

623^b

303