Interhospital conference Chaing Mai University th February 8

Interhospital conference Chaing Mai University th February 8 , 2011

Physical examination • 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 mm. Hg • 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 examination • 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 examination • Heart: regular rhythm, normal S 1 and S 2, 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 examination

Problem list 1.

Differential diagnosis 1.

1 2 3 4 5 6 7 8 9

Complete blood count • Hb 15 g/d. L, Hct 45%, • WBC 60, 320 cells/mm 3, neutrophil 29%, lymphocyte 23%, blast 44%, • platelet 105, 700/mm 3

Peripheral blood smear

Bone marrow aspiration

Bone marrow aspiration • Flow cytometry: slightly positive CD 34 and CD 41

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

Discharge exam (lesion on face) • Wright stain:

Thyroid function test • TSH 19 m. IU/L (3. 2 -43. 6), FT 4 1. 3 ng/d. L (2 -4. 9) (day 2) • Repeat TSH 26. 44 m. IU/L (1. 7 -9. 1), FT 4 1. 34 ng/d. L (0. 9 -2. 6) (day 11)

Liver function test • Total protein 4. 7 g/d. L, Albumin 2. 8 g/d. L, Globulin 1. 9 g/d. L, Cholesterol 125 mg/d. L AST 48 U/L, ALT 3 U/L, Alk Phos 122 U/L, TB 16. 1 mg/d. L, DB 0. 6 mg/d. L

Chemistry • Creatinine 0. 55 mg/d. L, • Na 140 mmol/L, K 4. 7 mmol/L, Cl 108 mmol/L, HCO 3 20 mmol/L • Ca 9. 7 mg/d. L, P 2. 5 mg/d. L, Uric acid 4. 2 mg/d. L

Chest 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 • (6/9/2010) moderate VSD 4 X 5 mm in size, bidirectional shunt PG 5 mm. Hg, pericardial effusion 6 mm • (15/9/2010) moderate to large VSD 5 X 6 mm, left to right shunt PG 15 mm. Hg, 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 diagnosis • Chromosome study: 46, XX, der(21; 21), +21 • Down syndrome with transient myeloproliferative disorder (TMD)

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/d. L) 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 (/mm 3) 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 (/mm 3) 81, 000 120, 000 209, 000 124, 000 116, 000 83, 000

Skin involvement in congenital leukemia • Found 80% of congenital leukemia • Skin nodule called “leukemia cutis” • 67% are classified in FAB M 4/M 5 Sung TJ, Lee DH, Kim SK, et al. J Korean Med Sci. 2010: 945 -9.

Skin involvement in 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: 869 -871.

Skin involvement in TMD • The skin lesions diminished spontaneously in all reported cases (median 1 month) • A cytological smear preparation is required Uhara H, Shiohara M, Baba A, et al. J Am Acad Dermatol. 2009: 869 -871.

Transient myeloproliferative 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 maifestations of TMD • 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 myeloproliferative disorder (TMD) • 30% of DS infants with TMD develop acute megakaryoblastic leukemia (AMKL) within 3 years • Presence of trisomy 21 and GATA 1 mutations is adequate for the excessive proliferation of megakaryoblasts seen in TMD Gurbuxani S, Vyas P, Crispino JD. Blood. 2004: 399 -406.

GATA-1 • GATA 1 normally promotes the development of megakaryocytes, erythroid cells, mast cells, and eosinophils • GATA 1 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 parameters of TMD Parameters Clinical: prematurity, ascites, bleeding Laboratory: • WBC > 100, 000/mm 3, • Severe coagulopathy, • Progressive liver failure, • No complete remission by 3 months Malinge S, Izraeli S, Crispino JD. Blood. 2009: 2619 -28.

Treatment of TMD • Observation in most cases • In cases with poor prognostic parameters, lowdose cytarabine (Ara-C 1 mg/kg/day for 7 days) may be beneficial Klusmann JH, Creutzig U, Zimmermann M, et al. Blood. 2008: 2991 -8.

Thank you for your attention