This is a case report of a dengue patient who developed hemophagocytic lymphohistiocytosis ( HLH).

1. Thursday Clinical
Presentation
Dr. Nigher Shultana
MD, Phase B resident
Department of Internal Medicine Unit -ƖƖ

2. Presenting complaints
A 22-year-old male non-diabetic, normotensive
student hailing from Jagannath hall of DU, was
admitted under department of Internal Medicine on
31.10.21 with the complaints of
-Fever for three days
-Generalized body ache for same duration
-Nausea and vomiting for same duration

3. History of present illness
According to the patient’s statement, he was in his
usual state of health 3 days prior to admission,
then he developed fever. Fever was high grade,
highest recorded temperature 1040F, didn't
fluctuate more than 1°F and didn’t touch the
baseline. There was no H/O chills and rigor or
profuse sweating, not relieved by taking
paracetamol.

4. Patient had generalized body ache and joint pain
without any evidence of joint swelling and joint
tenderness. Patient complained of headache and
retro-orbital pain without altered level of consciousness
and convulsion. Patient also had nausea and vomiting
for same duration without abdominal pain. Vomiting
was non–projectile, contained undigested food
materials but not blood and bile stained.

5. There was no H/O cough, burning sensation during
micturition. Patient denied any H/O gum bleeding,
epistaxis, passage of blood with stool. As it was
endemic period for dengue on that time, patient did
dengue NS1 antigen test by himself and was found to
be positive. His bowel and bladder habit were normal.

6. Past History
Nothing significant
Personal History
Non smoker, non- alcohol or drug- abuser

7. Family History
There was no significant family history
Drug History
Nothing significant

8. GENERAL EXAMINATION

9. • Appearance: Looked ill
• Body built : Average
• Anemia
• Jaundice
• Cyanosis
• Clubbing
• Koilonychia
• Leukonychia
• Edema
• Dehydration
Absent

10. • Neck vein: Not engorged
• Thyroid gland: Not enlarged
• Lymph Nodes: Not palpable
• Skin Condition: Diffuse blanching
maculopapular rash over the trunk
• Tourniquet test: Negative

11. • Temperature: 102⁰F
• Pulse: 110 beats/ min
• BP: 110/70 mmHg ( sitting)
• 110/80 mmHg ( standing)
• Respiratory rate: 18 breaths/min
• SPO2 : 98% in room air

12. SYSTEMIC EXAMINATION

13. Gastrointestinal system
• Lips, gums, teeth, tongue and oral cavity- Normal
• Abdomen:
• Inspection: Normal
• Palpation: Non tender in region
No palpable mass
No organomegaly
• Percussion: Tympanic, no shifting dullness
• Auscultation: Bowel sound- Normal
• DRE: Not done

14. Respiratory system
Inspection:
Shape of the chest: Normal
Palpation:
Trachea: Central in position
Apex beat: Left 5th intercostal space, 9cm from mid-sternal
line
Chest expansion- B/L symmetrical
Vocal fremitus: Normal
Percussion : Resonance
Auscultation:
Breath sound: Vesicular breath, no added sound
Vocal resonance: Normal

15. Cardiovascular system
Pulse: 110b/min, high volume, regular
Blood pressure: 110/70 mmHg( no postural drop)
JVP: Not raised
Precordium Examination:
Inspection: Normal
Palpation:
Apex beat in left 5th intercoastal space,9 cm from
midline
Palpable P2 and left parasternal heave-absent
Thrill-absent
Auscultation:1st and 2nd heart sound-audible, No
murmur

16. Nervous system
• Higher psychic function:
Conscious and oriented with normal speech.
• Cranial nerves: Intact
• Motor system:
Muscle tone: Normal
Muscle power: 5//5 on both upper & lower limb
(proximal and distal)
Reflexes: Normal
• Sensory system: Intact
• Cerebellar function and gait: Normal
• Fundoscopy: Normal

17. Salient features
A 22-year-old non-diabetic, normotensive Dhaka
University student was admitted under department of
Internal Medicine unit-2 with the complaints of high
grade, continued fever for 3 days, Highest recorded
temperature was 1040F along with nausea and
vomiting. Patient also had generalized body ache
,headache retro orbital pain and joint pain.

18. There was no H/O abdominal pain, hematemesis,
neck rigidity, altered level of consciousness,
convulsion, evidence of arthritis, cough, burning
sensation during micturition. Patient denied any H/O
gum bleeding, epistaxis, passage of blood with stool
and travelling to malaria endemic zone. He became
dengue NS1 antigen positive on his 3rd febrile period.

19. On general examination, patient was ill looking, diffuse
blanching maculo-papular rash over the trunk, pulse-
110b/min, temperature-102°F, respiratory rate-18
breaths/min, blood pressure-110/70mmHg,no postural
drop.
On systemic examination- no significant abnormality
was detected.

20. Diagnosis
Dengue Fever

21. Investigation

22. • Dengue NS1 antigen(outside)- Positive (31/10/2021)
• CBC- Hb%- 14.1 gm/dl
HCT- 35.5%
WBC-2.60/cmm
Platelet-136×10^9/ cu mm
• SGPT- 29U/L
• SGOT- 55U/L
• S.Creatinine- 0.8mg/dl
• Blood grouping - B Positive
• Urine R/M/E- Normal
• CRP- 44.6mg/L
• Xray Chest P/ A view- Normal(31/10/2021)

23. Treatment
1. Adequate oral fluid
2. Antipyretic
3. Anti emetic

24. Hospital course……

25. On 6th febrile period:
-Persistent high grade fever
-Shortness of breath
-Abdominal discomfort
O/E-
Jaundice- Present
Temperature-103°F
Tourniquet test- Positive
SPO2- 94 in room air
BP-110/80mmHg (lying position)
90/65mmHg (standing position)
features suggestive of B/L pleural effusion and
ascites

26. Date Hb
g/dl
HCT WBC/cmm PLT/cmm
3/11/2021 14.6 36.5 3800 39000
4/11/2021 14.8 38.1 4190 37000
5/11/2021 14.3 38.5 4280 36000
Date SGOT
U/L
SGPT
U/L
S. Bil
mg/dl
Total
protein
S.
Albumin
4/11/21 13189 2471 2.1
5/11/21 8485 1647 3.2 42.7 23.2

27. • PT with INR - 19.8 with 1.50 ( Prolonged)
• APTT - 48.5 sec (Prolonged)
• HBsAg - Negative
• Anti HCV - Negative
• Anti HEV IgM and IgG - Negative
• S. Electrolyte – Na- 128
K- 3.5
CL- 113
TCO2- 22

28. • Serum Creatinine - 0.9 mg/dl(N)
• Urine R/M/E – Normal
• ECG - Sinus Tachycardia
• Troponin - I - <0.002ng/ml(N)
• NT Pro BNP – 430 pg/ml(N)
• CRP- 63.4 mg/L
• Pro calcitonin- 9.7 ng/ml
• RT PCR for Covid 19- Negative

30. • Chest X-ray A/P view - B/L pleural effusion
• USG of W/A - Mild to moderate ascites
B/L mild pleural effusion
• Blood for Culture- Sent
• Urine for Culture- Sent

31. On 5th November(on 8th febrile period)
Patient became drowsy, confused and disoriented
Temperature- 105°F
Pulse- 120 beats/min
BP- 90/60mmHg
GCS- 8/15

32. Patient shifted to ICU

33. Date Hb HCT WBC PLT
6/11 14.7 38.1 7980 78000
7/11 12.7 32.9 7160 165000
8/11 13.0 34.9 6410 247000
10/11 12.9 36.0 4210 287000

34. Date SGPT SGOT S.Bili ALK
PHOS
S.Albu
min
TP
5/11 1647 8485 3.2 160
6/11 1171 2.9
8/11 526 1042 2.4 191 23.2 42.7
Date Plasma
Amonia
(9-30)
Lactic
acid(3.6-
18)
S.Creatin
ine
S. Urea
mg/dl
Pro Cal
ng/ml
5/11 13.8 81.2 1.5 56 9.7
6/11 1.3 51
8/11 35.0 36.9 1.0 39 3.63
9/11 16.0 43

36. • Urine R/M/E :(7/11/21)
Pus cell- 3-5/HPF
Epi cell- 0-3/HPF
RBC- 6-10/HPF
• Blood for C/S- Negative( 2 sample)
• Urine for C/S- Negative
• PT with INR – Prolonged
• APTT- Prolonged

37. On 12th febrile period
Patient was shifted to ward
-Persistent high-grade fever.
-Developed feature of worsening ascites and pleural
effusion.

38. On examination
Temperature: 102⁰F
Pulse: 110 rate: 22 breaths/min
SPO2 -98%
• Anemia
• Jaundice
• Ascites
• Hepato - Spenomegaly
• B/L pleural effusion
• GCS 12/15

39. Date Hb WBC Platelet
10/11 12.9 4210 287000
13/11 11.3 2650 272000
15/11 10.4 2670 326000

40. DATE CRP PROC
AL
LDH FERRI
TIN
D-
Dimer
10/11 44.6 11.9 3406 15769 13.18
12/11 96.4 4.17
15/11 86.2 4.0 1825 14757

41. DATE SGPT SGOT S.BILI ALBU
MIN
TP Alk
phos
10/11 263 428 2.5 26.7 50.8 158
11/11 29.4 53.2

42. DATE TCHOL HDLC LDLC TG
7/11 44 10 14 132

43. • ICT for Malaria- Negative
• Tipple antigen- Negative
• PBF- Mild normocytic normochromic anemia with
leucopenia
• USG of W/A-
Bilateral moderate pleural effusion
Moderate to marked ascites.
Hepatosplenomegaly with grade 1 fatty change

45. • Echocardiogram-
No RWMA, no vegetation
Good LV systolic function
Mild pericardial effusion
• Ascitic Fluid Study- Cytology- No malignant cell
Glucose – 6.6
Protein – 29.4
LDH- 1270
WBC-45 cell
Lymphocyte- 90%
RBC- plenty
ADA- 29.7

46. Problem list
• Dengue NS1 positive patient
• Persistent high grade fever for 15 days in spite of
taking broad spectrum antibiotic
• Presence of hepatosplenomegaly+ ascites+ B/L
pleural effusion+ altered mental status
• Ascitic fluid – exudative
• Blood C/S, Urine C/S, Tripple antigen, ICT for
malaria- negative
• Persistent pancytopenia
• Worsening of inflammatory markers

47. ??

48. Differential diagnosis
• Hemophagocytic syndrome with DHF
• Cytokine Storm with DHF
• MAS with DHF
• DIC with DHF

49. Investigation
• Bone marrow study- features suggestive
secondary reactive marrow with hyperplastic and
dysplastic changes in all three cell lineages.
• Fibrinogen level- 0.5g/L
• Serum LDH- 3406U/L
• Serum Triglyceride 278

50. Final Diagnosis
Hemophagocytic syndrome with DHF

51. Treatment
• Tab. Dexamethason 4mg for 8 weeks (than
gradually tapering the dose)
• PPI
• Calcium supplement

52. Follow Up
• Fever subsided after 2 days
• Patient condition improved dramatically
• 1 week later we follow up patient where patient
condition was improved both clinically and
biochemically.

53. Date SGPT SGOT S. BILI ALBU
MIN
TP ALK
PHOS
15/11 114 134 1.9 32.3 61.2 152
DATE PROCA
L
D-
DIMER
16/11 2.8 11.84

55. DISCUSSION REGARDING HLH:
- Rare, life-threatening disorder characterized by tissue
destruction due to abnormal immune activation.
- fever and multi-organ dysfunction, which is often
mistaken for sepsis.
- characterized by excessive macrophage activation
and cytokine release due to a failure in natural killer
cell function.
- Cause:Immune dysregulation and unchecked
inflammation.

56. 1. Infection
2. Malignancy
(e.g. Lymphoma)
3. Autoimmune
(e.g. Systemic JIA)
4. Immunodeficiency
Condition associated with HLH

57. Five of the following eight findings:
• Fever more than 38.5
• Splenomegaly
• PBF blood cytopenia, with at least two of the
following : HB < 9G/dL;platelet < 100000/
microl:absolute neutrophil count <1000/microL
• Hyper5triglyceridemia(fasting TG >265mg/dL) and/
or hypofibrinogenemia(<150mg/dl)
• Hemophagocytosis in bone marrow, spleen, lymph
node,or liver
• Low or absent nk cell activity
• Ferritin > 500ng/mL
• Elevated soluble CD25

58. • Example of others we would be likely to treat include
the following:
• A patient with CNS symptoms ,fever, cytopenias , and
ferritin >3000ng/ml or rapidly rising ferritin or elevated
sCD25
• A patient with CNS symptoms ,hepatitis, coagulopathy
and ferritin >3000ng/ml or rapidly rising ferritin or
elevated sCD25
• A patient with hypotension, fever, no response to broad
spectrum antibiotics and ferritin >3000ng/ml or rapidly
rising ferritin or elevated sCD25

59. 1.Approach varies depending upon trigger
2.Dexamethason
3.Etoposide
3.In mild cases associated with infection and
autoimmune disease-treat the underlying cause
4.Option for severe case-
Anakinra,IVIg,Rituximab,tacrolimus
5.+/- intrathecal methotrexate(CNS involvement)
6.In refractory case :Hemapoietic cell
transplantation.
Treatment of HLH:

60. Take home message
1.Dengue may present as various form such as
classical dengue, dengue haemorrhagic fever,
dengue shock syndrome, expanded dengue
syndrome.
2.When fever don’t subside with systemic
inflammatory response syndrome, we can suspect
expanded dengue syndrome with HLH.
3. Treatment with steroid shows dramatic response.

66. THANK YOU