Interhospital conferenceChaing Mai University

February 8th, 2011

Identification dataIdentification data• ผู้��ป่�วยทารกเพศหญิ�ง ลู�กคร��งไทย-อั�งกฤษ

อัาย� 5 ว�น ภู�มิ�ลู"าเนา จ.เชี%ยงใหมิ'

Chief complaintChief complaint• ผู้��ป่�วยมิ%ผู้(�นท%�หน�าแลูะตั�ว 3 ว�นก'อันมิาโรง

พยาบาลู

Present illnessPresent illness• ป่ระว�ตั�มิารดา

มิารดาอัาย� 30 ป่/ G2P1021 GA 37+6 weeks Blood group A Rh+ve antiHIV neg HBsAg neg ชี'วงตั�0งครรภู1มิารดาแข็3งแรงด% ไมิ'มิ%ไข็�อัอักผู้(�น ไมิ'มิ%ภูาวะแทรกซ้�อันอั(�นๆ ระหว'างตั�0งครรภู1 มิารดาคลูอัด normal delivery

Present illnessPresent illness• ป่ระว�ตั�ผู้��ป่�วย

แรกเก�ดน"0าหน�ก 2,555 g Apgar 9, 10 หลู�งเก�ดด�ดนมิแมิ'ได�ด% เร��มิมิ%ผู้(�นแดงท%�เป่ลู(อักตัาตั�0งแตั'ว�นท%� 2 หลู�งเก�ด ตั'อัมิากลูายเป่6นแผู้ลูถลูอัก แลูะเป่6นผู้(�นแดงข็�0นตัามิหน�า ลู"าตั�ว ตัอันท%�เร��มิมิ%ผู้(�นไมิ'มิ%ไข็�แลูะย�งด�ดนมิได�ด%

Present illnessPresent illness• อัาย� 3 ว�น มิ%อัาการตั�วเหลู(อัง on

phototherapy (bilibed) 1 ว�น microbilirubin (MB) ก'อัน discharge 13.3 mg/dL (อัาย� 86 ชี��วโมิง) หลู�ง discharge ย�งด�ดนมิแมิ'ได�ด% ถ'ายเหลู(อัง ผู้(�นเท'าเด�มิ

• ว�นน%0 (อัาย� 5 ว�น) น�ดมิาตั�ดตัามิเร(�อังตั�วเหลู(อัง ตัรวจพบผู้(�นมิากข็�0น ผู้��ป่�วยมิ%ไข็�ตั"�าๆ แตั'ย�งด�ดนมิได�ด%

Family historyFamily history• มิ%พ%�ชีายตั'างบ�ดา 1 คน อัาย� 8 ป่/ สุ�ข็ภูาพแข็3งแรงด% • ป่ฏิ�เสุธคนในครอับคร�วมิ%ผู้(�นเหมิ(อันก�บผู้��ป่�วย • ป่ระว�ตั�มิะเร3งแลูะโรคเลู(อัดในครอับคร�ว

Physical Physical examinationexamination• GA: a female neonate, active, jaundice zone 3, BW 2,550 g• V/S: PR 140/min, T 36.7 °C,

RR 52/min, BP 75/55 mmHg• Skin: generalized erythematous papules and some pustules, spare both palms and soles, erythematous plaque with abrasion and crust on top on lower eye lids and cheeks both sides

Physical Physical examinationexamination• HEENT: no pale conjunctivae, icteric sclera, no conjunctivitis, no discharge per both eyes, tympanic membrane intact both sides, pharynx no injection• Lymph nodes: cervical, supraclavicular, axillary and inguinal lymph nodes were not palpable

Physical Physical examinationexamination•Heart: regular rhythm, normal S1 and S2, no murmur •Lungs: clear and equal, no adventitious sound•Abdomen: liver 2 cm below right costal margin, liver span 6 cm, spleen just palpable, soft, no mass•Genitalia and anus: normal appearance

Physical Physical examinationexamination

Problem listProblem list1.

Differential Differential diagnosisdiagnosis1.

11 22 33

5544 66

77 88 99

Complete blood Complete blood count count • Hb 15 g/dL, Hct 45%, • WBC 60,320 cells/mm3,

neutrophil 29%, lymphocyte 23%, blast 44%, • platelet 105,700/mm3

Peripheral blood smearPeripheral blood smear

Peripheral blood smearPeripheral blood smear

Bone marrow aspiration Bone marrow aspiration

Bone marrow aspiration Bone marrow aspiration

Bone marrow aspiration Bone marrow aspiration

Bone marrow Bone marrow aspirationaspiration

• Flow cytometry: slightly positive CD34 and CD41

Discharge exam Discharge exam (lesion on face)(lesion on face)• Gram stain: no organism• Discharge culture: - Rare Viridan Streptococci - Rare Coagulase-negative Staphylococci

Discharge exam Discharge exam (lesion on face)(lesion on face)• Wright stain:

Thyroid function Thyroid function testtest• TSH 19 mIU/L (3.2-43.6), FT4 1.3 ng/dL (2-4.9) (day2) • Repeat TSH 26.44 mIU/L (1.7-9.1), FT4 1.34 ng/dL (0.9-2.6) (day 11)

Liver function Liver function testtest• Total protein 4.7 g/dL, Albumin 2.8 g/dL, Globulin 1.9 g/dL, Cholesterol 125 mg/dL AST 48 U/L, ALT 3 U/L, Alk Phos 122 U/L, TB 16.1 mg/dL, DB 0.6 mg/dL

ChemistryChemistry

• Creatinine 0.55 mg/dL,• Na 140 mmol/L, K 4.7 mmol/L, Cl 108 mmol/L, HCO3 20 mmol/L • Ca 9.7 mg/dL, P 2.5 mg/dL, Uric acid 4.2 mg/dL

Chest Chest radiograph: radiograph: • The heart size is enlarged. The mediastinal contour is normal. No significant infiltration in the lungs. The bony thorax is intact. The visualized bowel gas pattern is normal.

Echocardiography Echocardiography • (6/9/2010) moderate VSD 4X5 mm in size, bidirectional shunt PG 5 mmHg, pericardial effusion 6 mm• (15/9/2010) moderate to large VSD 5X6 mm, left to right shunt PG 15 mmHg, moderate to large amount of clear pericardial effusion 5 mm, LV free wall in diastolic phase pericardial effusion posterior wall of LV apex 1.5 cm

Final diagnosisFinal diagnosis • Chromosome study: 46, XX, der(21;21), +21

• Down syndrome with transient myeloproliferative disorder (TMD)

Progression Progression • Wait and observe• Plalelet transfusion 1 time• Skin lesion was gradually improved by - Oral Cephalexin - Wound dressing

Date 21/9

24/9 25/9 1/10 6/10 28/10

Hb (g/dL)

11.7

13.2 10.5 13.4 9.6 9.7

Hct (%)

36.5

40.0 31.6 43.1 28.6 28.8

WBC (/mm3)

33,600

33,200

22,100

20,600

11,700

7,000

Neut (%)

18 14.3 29 11.7 30 20.5

Blast (%)

56 present

43 present

28 absent

Plt (/mm3)

81,000

120,000

209,000

124,000

116,000

83,000

Skin involvement Skin involvement in congenital in congenital leukemia leukemia • Found 80% of

congenital leukemia• Skin nodule called “leukemia cutis”• 67% are classified in FAB M4/M5

Sung TJ, Lee DH, Kim SK, et al. J Korean Med Sci. 2010: 945-9.

Skin involvement Skin involvement in TMDin TMD

• Total of 16 patients with trisomy 21 accompanied by skin lesions have been reported to date• The face was the most common site of skin lesions

Uhara H, Shiohara M, Baba A, et al. J Am Acad Dermatol. 2009: -869871

.

Skin involvement Skin involvement in TMDin TMD

•The skin lesions diminished spontaneously in all reported cases (median 1 month)• A cytological smear preparation is requiredUhara H, Shiohara M, Baba A, et al. J

Am Acad Dermatol. 2009: -869871

.

Transient Transient myeloproliferativmyeloproliferative disorder (TMD)e disorder (TMD)• A disease in which immature megakaryoblasts accumulate in liver, bone marrow, and peripheral blood• Found 10% of infant with Down syndrome• Spontaneous remission in most cases

Gurbuxani S, Vyas P, Crispino JD. Blood. 2004: 399-406.

Clinical Clinical maifestations of maifestations of TMDTMD• Elevated white blood cell with hepatomegaly• Hydrops fetalis• Jaundice• Bleeding diathesis• Respiratory distress with ascites• Pleural effusion• Signs of heart failure• Skin infiltrates

Malinge S, Izraeli S, Crispino JD . Blood. 2009:2619-28.

Transient Transient myeloproliferativmyeloproliferative disorder (TMD)e disorder (TMD)• 30% of DS infants with TMD develop acute megakaryoblastic leukemia (AMKL) within 3 years• Presence of trisomy 21 and GATA1 mutations is adequate for the excessive proliferation of megakaryoblasts seen in TMD

Gurbuxani S, Vyas P, Crispino JD. Blood. 2004: 399-406.

GATA-1GATA-1 • GATA1 normally promotes the development of megakaryocytes, erythroid cells, mast cells, and eosinophils• GATA1 mutation providing a block in megakaryocytic differentiation → AMKL• Spontaneous regression of TMD could then be explained by the loss of a permissive fetal hematopoietic environment

Gurbuxani S, Vyas P, Crispino JD. Blood. 2004: 399-406.

Poor prognostic Poor prognostic parameters of TMDparameters of TMD

Parameters Clinical: prematurity, ascites, bleedingLaboratory: • WBC > 100,000/mm3, • Severe coagulopathy, • Progressive liver failure,• No complete remission by 3 months

Malinge S, Izraeli S, Crispino JD . Blood. 2009:2619-28.

Treatment of Treatment of TMDTMD• Observation in most cases• In cases with poor prognostic parameters, low- dose cytarabine (Ara-C 1 mg/kg/day for 7 days) may be beneficial

Klusmann JH, Creutzig U, Zimmermann M, et al. Blood. 20082991: -8.