This document describes the case of a 1-year-old boy who presented with prolonged fever for 10 days. Investigations revealed hepatosplenomegaly, anemia, thrombocytopenia, and elevated inflammatory markers. Echocardiography showed a right coronary artery aneurysm, suggestive of atypical Kawasaki disease. Bone marrow examination showed hemophagocytosis. The patient was diagnosed with atypical Kawasaki disease complicated by secondary hemophagocytic lymphohistiocytosis (HLH). Treatment with intravenous immunoglobulin and aspirin led to improvement of symptoms and regression of organomegaly within a week. Follow up showed no abnormalities. The document discusses that 1.9% of Kawasaki

1. AN UNUSUAL CASE OF
PROLONGED FEVER
SPEAKER - Dr. GNANDAS BARMAN

2. Pritwish
Mondal
1 year old
Male/Hindu
child from
Bongaon
Admitted on
07/09/2014

3. •Fever and excessive irritability for -10 days

4. H/O Present illness
Patient developed high grade continous fever 1o days
prior to admission.
Associated redness of both eyes.
Fever was not associated with rigor, cough, rash,
dysuria, altered sensorium, convulsion.
The child was extremely irritable since the onset of
fever.

5. On Examination:
 Alert and irritable.
 Vitals- PR-140/min,
BP-80/44mm of Hg,
RR-36/min,
Temp-104.2⁰F,
CRT-2 sec
SpO2-97% in room air.
 AF- closed
 Bilateral bulbar conjunctival congestion.
 Pallor present

6. On Examination:
 Multiple right posterior cervical
lymphadenopathy-
1.5cm, firm, discrete, mobile , nontender.
 No rash /desquamation.

7. On Examination:-
 Anthropometry: -
Wt- 10.5 Kg (between 50th - 85th percentile)
Length - 78cm (50th - 85th percentile)
Head circumference-45 cm (15th - 50th
percentile)

8. G.I. SYSTEM-
 UPPER G.I.- normal
 Liver -4 cms along Rt MCL , liver span-
10 cms, firm, sharp margin, non tender,
left lobe not palpable.
 Spleen-3 cms
 Other systems- WNL

9. Differential Diagnosis
 VIRAL FEVER.
 HEMATOLOGICAL MALIGNANCIES.
 KAWASAKI DISEASE

10. INVESTIGATIONS (7/9/14):
 CBC-
Hb: 6 gm%
TLC: 20,000/ cu mm, (N60/L36/M2/E2)
Platelet: 50,000/cumm
ESR- 25 mm,
no abnormal cells in peripheral smear.

11.  LFT: TSB-0.6,
ALT/AST-80/68,
Alb-2.6,Glb-2.8
Urea/Creatinine-22/0.8
Serum electrolytes-Na/K- 142/4.7
Urine RE/ME: 5-6 pus cells.

12. MPslide, MPDA- Negative
DengueIgM-NR
Widal- Negative.

13.  Urine and blood c/s sent.
 Mantoux testdone.
 Chest Xray-WNL
 USG W/A-Hepatosplenomegaly

14. Treatment:-
 IV Fluids
 Inj Ceftriaxone
 Syr Paracetamol
 PRBC transfusion

15. Child toxic and having high grade fever.
INVESTIGATIONS -
 Blood and urine cultures- sterile,
 Mantoux- negative
 CSF -04 lymphocytes/cu mm, sugar-80 mg/dl,
protein-24mg/dl, ADA- 0.9.
 CBC –Hb -10.5 gm% TLC- 22,000 (N62 L32 E2 M4)
Platelets-48,000/cmm,

16.  Bone marrow aspiration study done.

17. 11/9/14
ECHOCARDIOGRAPHY-
RIGHT CORONARY ARTERY ANEURYSM{6mm}
LVEF-52%; mild LV systolic dysfunction.
No valvular regurgitation or pericardial effusion.
- Highly suggestive of Kawasaki disease.
PBS platelets-45,000

18. ON 12/09/14
 Serum Ferritin-1886 ng/ml(>500)
 Triglyceride-442mg/dl(>265 )
 Fibrinogen-119.6mg/dl(<150)

19. BONE MARROW STUDY-
Bone marrow examination
showing
Hemophagocytosis

20. PROPOSED HLH DIAGNOSTIC
CRITERIA,2009:
[1] Molecular diagnosis of hemophagocytic
lymphohistiocytosis(HLH) or X-linked lymphoproliferative
syndrome (XLP).
[2] Or at least 3 of 4:
 a. Fever
 b. Splenomegaly
 c. Cytopenia (minimum 2 cell lines reduced)
 d. Hepatitis

21. PROPOSED HLH DIAGNOSTIC
CRITERIA,2009:
[3]. And at least 1 of 4:
 a. Hemophagocytosis
 b. ↑ Ferritin
 c. ↑ sIL2Rα (CD25)
 d. Absent or very decreased NK function
[4]. Other results supportive of HLH diagnosis:
 a. Hypertriglyceridemia
 b. Hypofibrinogenemia
 c. Hyponatremia
Filipovich A et al[ASH Education Book Jan 1,2009 vol.2009 no.
1 127-131]

22. DIAGNOSIS
ATYPICAL KAWASAKI DISEASE WITH SECONDARY
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS[HLH]

23. TREATMENT
 IV IMMUNOGLOBULIN- 2gms/kg transfused over 24
hours on 13/9/14.
 Platelet count-80,000 on 14/9/14
 CBC on 15/9/14 : Hb-11, Tc-12,000,N52L42B5E1
platelets-1.5 lakh
 Aspirin 80 mg/kg started from 15/9/14.

24.  Patient became afebrile 36 hrs after IVIG transfusion.
 Hepatosplenomegaly started to regress within 3 days
of IVIG transfusion

25. Follow up
@6 wks
Echo-normal coronaries Aspirin stopped
Aspirin continued for 6 wks @5mg/kg/day
Two weeks later
Echo –no abnormality Aspirin dose reduced to 5 mg/kg/day

26. DISCUSSION
1.9% of children with acute kawasaki disease are
reported to develop secondary HLH.†
It result from cytotoxic dysfunction leading to
persistent expansion of T cells and Macrophages ,
escalating production of proinflammatory
cytokines.
†Latino et al[ J Pediatr Hemato Oncol 2000 oct;32(7):527-31]

27. Present with prolonged and persisting fever beyond initial
IVIG treatment ; KD complicated with secondary HLH is
difficult to distinguish from refractory KD/ recurrent KD.
Onset of secondary HLH or MAS with mean of 13.3 days
[range 3-22 days];
However recurrent KD typically occurred much later at a
mean of 17.9 months[range 1-60 months]‡
Treatment includes Pulse Methyl Prednisolone, Anakinra,
Etoposide.
‡ Kang et al[Blood Res. 2013 Dec; 48(4): 254–257]

28. CASE
SERIES
PATIENTS OF KD
COMPLICATED WITH
HLH
RESPONSIVE
TO IVIG
ADDITIONAL
IMMUNOMODULATOR
REQUIRED
1. 12 1 11
2. 8 1 7