kawasaki with hlh,an unusual case of fever

AN UNUSUAL CASE OF PROLONGED FEVER

SPEAKER - Dr. GNANDAS BARMAN

Pritwish Mondal1 year old Male/Hindu child fromBongaonAdmitted on 07/09/2014

Chief Complaints: •Fever and excessive irritability for -10 days

H/O Present illnessPatient 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.

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

On Examination:Multiple right posterior cervical

lymphadenopathy- 1.5cm, firm, discrete, mobile ,

nontender.No rash /desquamation.

On Examination:-Anthropometry: - Wt- 10.5 Kg (between 50th - 85th

percentile) Length - 78cm (50th - 85th percentile)

Head circumference-45 cm (15th - 50th percentile)

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

Differential DiagnosisVIRAL FEVER.

HEMATOLOGICAL MALIGNANCIES. KAWASAKI DISEASE

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.

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

MP slide, MPDA- Negative

Dengue IgM-NR

Widal- Negative.

Urine and blood c/s sent.

Mantoux test done.

Chest X ray- WNL

USG W/A-Hepatosplenomegaly

Treatment:-IV FluidsInj CeftriaxoneSyr ParacetamolPRBC transfusion

On 10/9/14

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,

Bone marrow aspiration study done.

11/9/14ECHOCARDIOGRAPHY- RIGHT CORONARY ARTERY

ANEURYSM6mmLVEF-52%; mild LV systolic dysfunction.No valvular regurgitation or pericardial effusion. - Highly suggestive of Kawasaki

disease.

PBS platelets-45,000

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

BONE MARROW STUDY-Bone marrow examination showing

Hemophagocytosis

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. Feverb. Splenomegalyc. Cytopenia (minimum 2 cell lines reduced)d. Hepatitis

PROPOSED HLH DIAGNOSTIC CRITERIA,2009:

[3]. And at least 1 of 4:a. Hemophagocytosisb. ↑ Ferritinc. ↑ sIL2Rα (CD25)d. Absent or very decreased NK function[4]. Other results supportive of HLH diagnosis:a. Hypertriglyceridemiab. Hypofibrinogenemiac. Hyponatremia

Filipovich A et al[ASH Education Book Jan 1,2009 vol.2009 no. 1 127-131]

DIAGNOSIS ATYPICAL KAWASAKI DISEASE WITH

SECONDARY HEMOPHAGOCYTIC

LYMPHOHISTIOCYTOSIS[HLH]

TREATMENTIV IMMUNOGLOBULIN- 2gms/kg

transfused over 24 hours on 13/9/14.

Platelet count-80,000 on 14/9/14CBC on 15/9/14 : Hb-11, Tc-

12,000,N52L42B5E1 platelets-1.5 lakh

Aspirin 80 mg/kg started from 15/9/14.

Patient became afebrile 36 hrs after IVIG transfusion.

Hepatosplenomegaly started to regress within 3 days of IVIG transfusion

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

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]

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]

1.Latino et al[ J Pediatr Hemato Oncol 2000 oct;32(7):527-31]

2. Wang et al[Semin Arthritis Rheumatism 2014 aug;44(4):283-304]

CASE SERIES

PATIENTS OF KD COMPLICATED WITH HLH

RESPONSIVE TO IVIG

ADDITIONAL IMMUNOMODULATOR REQUIRED

1. 12 1 11

2. 8 1 7

THANK YOU