貝氏症合併骨髓發育不良症候群之個案報告與病例分析

(1)

201

ၡāāࢋ

( Beh et's disease )

( myelodysplastic syndrome )

( chronic myelomonocytic leukemia )

( refractory anemia )

47XX ( tri-

somy 8 )

( 65% vs 3-36% ) ( 15% vs 21-75% )

( 77.8% vs 6.5-16.3% )

( 81.8% vs 71.4% )

( 63.6% vs 28.6% )

( 100% vs 71.4% )

(2)

͔֏

֓ͩা ( Beh et's disease, BD ) ߏ˘჌ঽЯ̙

ځ۞Бّ֗൴ۆ়ঽĂঽநܑனࠎҕგۆĂΞϚ

̈́ Б ֗ Ą ׎ ෧ ᕝ ߏ ֶ ᓜ Ԗ ̈́ ঽ ந প ᇈ Ă ॲ ፂ International Study Group ( ISG ) for Beh et's disease ٺ 1990 ѐٙࢎ̶̝ᙷᇾ໤Ăଈ۰υืѣೇ൴ّ

˾ටሚႹ ( ˘ѐ̰Ҍ͌൴ϠˬѨ˾ටሚႹ )Ăͷ д˭Еαีܑᇈ̚΍ன׌ีͽ˯ĂΒ߁ೇ൴ّϠ തጡሚႹăீొঽតăϩቲঽត̈́ϩቲ੫וീྏ

( pathergy test ) ӔวّĂ̖ਕ෧ᕝࠎ֓ͩা¹Ąѩ γĂώঽΞਕ΍ன۞ᓜԖܑனᔘΒ߁ᙯ༼ۆă̂

ҕგۆٕং๫ăৠགྷጯঽតăঐ̼྽ঽតăઘ༝

ۆă͕ҕგঽត̈́҈ቯ۱ొ۞ঽតĄ B51 ݭˠᙷ Ϩҕ஧ԩࣧ ( HLA-B51 ) ᄃ֓ͩা۞൴ঽதăᚑ ࢦޘ࠹ᙯĂдΟකྮડાĂΒ߁ڌֲăܠٛұ̈́

г̚ঔ઼छĂ֓ͩা۞ଈ۰ͧઉ૵ˠѣྵ੼ּͧ

૲ѣ HLA-B51 ( 55-81% vs 10-15% )ĂҭдҘ઼͞

छ่ѣࡗ 1 3 % ۞ଈ۰૲ѣѩૄЯĂͷ׶Ꭾঽத

ྵ൑࠹ᙯ²Ą

੻ល൴ֈ̙։া࣏ཏ ( myelodysplastic syndrome, MDS ) ߏ˘ཏ੻លౄҕΑਕள૱۞়ঽĂ

࿅ΝజჍࠎ݈Ϩҕঽ ( preleukemia ) ٕሕ᝚ّϨ ҕঽ ( smoldering leukemia )Ă̂ࡗѣ 30% ۞ଈ۰

ົᖼតࠎާّ੻លّϨҕঽ ( a c u t e m y e l o i d leukemia, AML )Ăॲፂ French-America-British ̶ ᙷր௚ ( FAB classification )³ĂΞ̶ࠎ࿱׽ّళҕ ( refractory anemia, RA )ă࿱׽ّళҕҡᒖېᜠ܂

஧ ( refractory anemia with ringed sideroblasts, RARS )ă࿱׽ّళҕҡ࿅ณ܂௟ࡪ ( refractory anemia with excess blasts, RAEB )ăᖼត̚۞࿱׽

ّళҕҡ࿅ณ܂௟ࡪ ( refractory anemia with excess blasts in transformation, RAEB-t )ăၙّ੻ល

ಏ८௟ࡪّϨҕঽ ( chronic myelomonocytic leukemia, CMMoL ) ඈ̣჌ֲݭĂ੻ល̰௟ࡪᇴ ϫϒ૱ٕᆧΐĂѣ dysplasia ன෪Ăҭ׹ᙝҕ୵

ੵ CMMoL ֲݭͽಏ८஧ᆧΐࠎপҒγĂӮΞ֍

Ҍ͌˘࣎րЕ۞ҕ஧ᇴϫഴ͌Ą

ώ̬͛௜˘࣎֓ͩা۞ଈ۰Ăд൴ঽ̱ѐޢ జ෧ᕝࠎ੻ល൴ֈ̙։া࣏ཏĂߖҒវ̶ژಡӘ ࠎ 47XX ׀ௐˣ၆ߖҒវˬវ ( trisomy 8 )Ąаᜪ

࿅Ν͛ᚥĂΒӣώঽּВ˟˩ּЪ׀֓ͩাᄃ੻

ល൴ֈ̙։া࣏ཏ۞ଈ۰Ă̶ژ׎ᓜԖܑன̈́ߖ Ғវள૱Ă൴னᄃΪ଀ז֓ͩাٕࣧ൴ّ੻ល൴ ֈ̙։া࣏ཏ۞ଈ۰ѣព඾मளĂ߇дѩ೩΍֭

ଣ੅׎Ξਕ̝፟טĄ

ঽּ̬௜

˘Ҝέ៉΍Ϡ۞ّ̃ঽଈĂٺ 4 1 ໐ॡொϔ اҝٺΐो̂Ă࿅Νઉ૵ଐԛ։рĄд 43 ໐ॡ

ࢵѨЯͅᖬ൴፵ă˾ට̈́ϠതጡሚႹҌ໢࣯ර۞

˘छгડᗁੰՐ෧ĂЯϩቲ੫וീྏ ( pathergy test ) วّĂజ෧ᕝࠎ֓ͩাćˬѐޢЯ޺ᜈّ൴

፵ҝੰĂ༊ॡҕ୵ᑭߤ൴னϨҕ஧ᆧΐ ( WBC 30.6 x 10⁹/L, neutrophils 72%, monocytes 11% )Ă ҕࡓ৵ ( 14.1 gm/dL ) ᄃҕ̈ڕ ( 243 x 10⁹/L ) ᇴ ࣃϒ૱Ă੻ល̷ͯ൴ன௟ࡪᇴϫᆧΐĂ༊ॡᗁर ᄮࠎΞਕߏ੻ល൴ֈ̙։া࣏ཏٕ੻លᆧϠ়ّ

ঽ ( myeloproliferative disorder ) ౄјĂҭ൑ڱቁ ؠ෧ᕝĄଈ۰ٺ 48 ໐ॡ˫Яᚑࢦཛ൭ăཛᕫ̈́

੼፵ГѨҝੰĂ̂བᙡᑭߤ൴னдਫ਼བϐბѣሚ Ⴙன෪Ă̷ͯᑭߤពϯ୽͐ᕭڽჸะă௡ᖐ஧ও ማ֭ԛј҇܂ཚĂܐՎ෧ᕝࠎҹษͩঽ ( Crohn's disease )Ă̙ضгĂЯབࡍ͋҃ତצొ̶ਫ਼བă

۠བăඕབ̷ੵ̈́བӚЪఙĂঽநಡӘពϯੵ˞

ሚႹᄃ҇܂ཚγĂдᕆቯ˭ҕგѣԊొ۞ܡ๫ّ

ᙯᔣෟĈ֓ͩা ( Beh et's disease )

੻ល൴ֈ̙։া࣏ཏ ( Myelodysplastic syndrome )

ၙّ੻លಏ८௟ࡪّϨҕঽ ( Chronic myelomonocytic leukemia ) B51 ݭˠᙷϨҕ஧ԩࣧ ( HLA-B51 )

ௐˣ၆ߖҒវˬវ ( Trisomy 8 )

(3)

જਔ̰ቯۆ ( focal obliterative endarteritis )ĂЯѩ జ෧ᕝࠎ֓ͩা࠹ᙯ̝ҕგۆĂдᙷ׽ዔڼᒚ˭

ঽଐԼචĄ

Я޺ᜈѣ൴፵̈́ཛ൭۞াېĂͷЪ׀׌઎។

ᙯ༼ᄃν઎ተᙯ༼ূ൭Ăଈ۰ٺ 49 ໐ॡаזέ

៉Ă֭ˢੰତצྎ௟۞ᑭߤĂநጯᑭߤ֭Ϗ൴ன ѣ˾ටٕϠതጡሚႹăீొࢆ૾ۆٕϩቲ۞ঽ իĂҭϩቲ੫וീྏ̪ࠎวّĂҕ୵ᑭߤពϯϨ ҕ஧ᆧΐ ( WBC 13.9 x 10⁹/L, neutrophils 68.3%, lymphocytes 21.5%, monocytes 9.2% )Ăҭҕࡓ৵ ( 14.6 gm/dL ) ̈́ҕ̈ڕ ( 159 x 10⁹/L ) ϒ૱Ă੻ល

̷ͯ൴ன௟ࡪᇴϫᆧΐĂ܂௟ࡪ ( b l a s t s ) Κ 3%Ă֭ѣࡓҕ஧Ϡј̙։ ( dyserythropoiesis ) ̈́ ᔺ௕஧Ϡј̙։ ( dysgranulopoiesis )ĂߖҒវᑭ ߤΞ֍ 21 ࣎ metaphase ௟ࡪӮࠎ 47XX ̈́ trisomy 8 Ă ॲፂ FAB ̶ᙷ³Ă෧ᕝࠎၙّ੻លಏ८௟ࡪّϨ ҕঽ ( CMMoL )Ăࠎ੻ល൴ֈ̙։া࣏ཏ۞˘჌

ֲݭĂЯଈ۰่ڇϡ࿅ൺഇ۞ᙷ׽ዔĂϏڇϡ࿅

ࡌͪ΅৵ă௟ࡪ߲୭ᘽۏٕ׎΁ҺࠪԺט጗Ă߇ ᛳٺࣧ൴ّ੻ល൴ֈ̙։া࣏ཏĂ҃ܧڼᒚ࠹ᙯ

ّ ( Ѩ൴ّ ) ੻ល൴ֈ̙։া࣏ཏĄΩγĂ̂བ ᙡᑭߤ̈́̈བᛷᇆពϯ൑߿જّঽիĂ८Ⴣౄᇆ ᑭߤ൴னᗕ઎۵੻ᐝ̈́ν઎۵γኺѣ৿ҕّᗼѪ ( avascular necrosis )ĂΠ઎។ᙯ༼ѣᙯ༼᎕୵Ă ෧ᕝࠎ֓ͩা࠹ᙯ۞੻ᗼѪᄃᙯ༼ۆĂฟؕග̟

prednisoloneᄃ azathioprine ۞ڼᒚĄ

ௐ˟ѐĂଈ۰Яᆐধᐝ൭ăཛ൭̈́਒൭జਖ਼ Ҍާ෧Ăநጯᑭߤ൴னវ໢ 38.5 ƨĂҕᑅ 80/40 mmHgĂͷα۳ДҽĂ၁រވᑭߤ۞ள૱൴னѣ Ϩҕ஧ᆧΐ ( WBC 14.9x10⁹/L, segmented neutrophil 68%, band form 18%, lymphocyte 4%, monocyte 10% )ă̂ҕ஧ّళҕ ( Hgb 10.5 gm/dL, M- CV 113.8 fL )ăࡓҕ஧Քࢫిத ( ESR ) 115mm at 1 houră C-ͅᑕకϨ ( CRP ) 33 mg/dL Ă࿪ཝᕝ ᆸᑭߤᘃႷѣർཝቯᐖਔᚭং๫ ( dural sinus thrombosis )ᄃ৿ҕّབ྽়ঽ ( ischemic bowel disease )ĂѩγĂ troponin-I ˯̿ă͕࿪ဦΞ֍

l e a d Iă a V L ă V 4 - 6 ѣ S T ၟ߱˯̿̈́ࣆཉ T گĂ௑Ъ͕҉ୟ๫۞෧ᕝĄଯീ఺ֱܑனߏ֓ͩ

া࠹ᙯ̝Бّ֗ҕგۆٙጱ࡭Ă֭ΞਕЪ׀ୀҕ

ّЃҹĂღާ૟ଈ۰ᖼҌΐ᜕ঽٗĂ֭ග̟̂ณ

ᙷ׽ዔ ( methylprednisolone ) ਔ኏ăᐖਔԩϠ৵ ᄃք৵ ( heparin ) ڼᒚĂҭঽଐ̪ϏԼචĂҝੰ

ௐˬ͇ॡ΍ன͘޽ᄃཙశ൴∆۞ன෪Ăͷޝԣಶ

ೋ̼Ҍᗼ৅Ă᎕ໂгΐ˯ᐖਔڦडҺࠪ஧కϨ ( intravenous immunoglobulin, IVIG ) ݈̈́Еཛྷ৵ E1 ( prostaglandin E1 ) ڼᒚĂ̪൑ព඾ड़ڍĂҕ

୵̚ D-dimer ᄃ FDP ˯̿Ă fibrinogen ̈́ҕ̈ڕ

˭ࢫĂ PT/aPTT ؼܜĂᘃႷߏᚢႝّҕგ̰጖ҕ ( disseminated intravascular coagulation, DIC )Ă̙

ضгĂଈ۰ٺҝੰௐ˩˝͇Я͕۱਽ა࿅͵Ą

͛ᚥ̶ژ̈́੅ኢ

аᜪ࿅Ν͛ᚥĂΒӣώঽּВѣ˟˩࣎Ъ׀

֓ͩাᄃ੻ល൴ֈ̙։া࣏ཏ۞ঽּ^{4 - 11}Ă׎̚

˩˛ּֽҋ͟ώĂҘ঱Ͱăᔹ઼̈́έ៉Ч˘ּĂ ଈ۰۞ૄώྤफ़ăᓜԖܑனᄃߖҒវ̶ژඕڍፋ நٺܑ˘Ąಶ൴ঽึԔֽᄲĂ֓ͩাΞ൴ঽٺ੻

ល൴ֈ̙։া࣏ཏ̝݈ăޢٕТॡĂଈ۰జ෧ᕝ ࠎ֓ͩাЪ׀੻ល൴ֈ̙։া࣏ཏ۞ѐ᛬̚Ҝᇴ ࠎ 47 ໐ ( range 10-74 ໐ )Ăྵࣧ൴ّ੻ល൴ֈ̙

։া࣏ཏଈ۰ѐ᛬ࡗ 60-75 ໐ࠎѐᅅ¹²Ă҃֓ͩ

াଈ۰ѐ᛬݋Ҳ۞кĂ఼૱д 20-40 ໐̝ม²Ą

ֶፂ FAB ̶ᙷ³Ăѩ˟˩࣎ঽּ̚ѣ˩˟ּᛳٺ RAĂߏҫ౵кᇴ۞˘჌ֲݭĂᄃ̂ొ̶ϏЪ׀

֓ͩা۞ࣧ൴ّ੻ល൴ֈ̙։া࣏ཏಡӘ࠹Ҭ

( ܑ˟ )^13-20Ă RARS ᄃ RAEB ֲݭЧˬּĂ˘ּ

ࠎ RAEB-t ֲݭĂώ͛ঽּ˜͵ࠧ˯ௐ˘࣎Ъ׀

CMMoL۞֓ͩাঽּಡӘĄ

੅ኢ˘ăЪ׀੻ល൴ֈ̙։া࣏ཏ۞֓ͩাଈ۰

̝ᓜԖܑன̶ژ

̶ژ˟˩ּЪ׀੻ល൴ֈ̙։া࣏ཏ۞֓ͩ

াଈ۰̝ᓜԖܑனĂֶፂ Beh et's Disease Research Committee of Japanٺ 2003 ѐޙᛉ۞࣒ࢎޢ֓ͩ

া෧ᕝᇾ໤²¹Ă˩ּ̣ ( 75% ) ᛳٺ̙ԆБݭ ( incomplete type )ĂႷҬݭ ( suspected type )ѣαּ

( 20% )ĂԆБݭ ( complete type )่˘ּ ( 5% )Ă

࿅Νᔹ઼ѣ׌࣎֓ͩা۞ࡁտϺ൴ன̙ԆБݭҫ

౵̂кᇴĂҭ׎ּͧ 33% ( 2001 ѐ )²²ᄃ 38%

( 1997ѐ )²³ྵԧࣇ̶ٙژ۞˟˩࣎Ъ׀੻ល൴ֈ

̙։া࣏ཏ۞ঽּࠎҲĂ൒҃఺׌࣎ࡁտٙଳϡ

۞̶ᙷ͞ڱࠎ࣒ࢎޢ Shimizu's classification²⁴Ă

(4)

ܑ˘Ĉ˟˩Ҝ֓ͩাЪ׀੻ល൴ֈ̙։া࣏ཏ ( MDS ) ଈ۰۞ૄώྤफ़ăᓜԖܑன׶ߖҒវ̶ژ

ঽ ѐ ّ MDS ߖҒវ Ϩ๫ͩঽ࠹ Ϩ๫ ˾ට Ϡത ீ ϩቲ ϩቲ ࢴ྽ ߃๫ ᙯ ৠགྷ HLA- ણ҂

̝ ௡ݭ ၆ٺMDS ͩঽ ྽ሚ ត ੫ו ٕབ ٕҕ ༼

ּ ᛬ Ҿ ֲݭ^a ( karyotype ) ۞ॡม^b ̶ݭ^cሚႹ Ⴙ ঽ តঽ ྏរ ሚႹ გۆ ۆ ঽត B51 ͛ᚥ

1 10 F RAEB 46,XX,ring 6 0 S + - - EN NA IU, EU - - - - 4

2 23 F RA 47,XX,+8 +5 yrs I + + - EN NA IU - - - - 7

3 25 M RA 47,XY,+8 +5 yrs I + + - EN NA IU - - - - 6

4 34 F RA 47,XX,+8 +3 yrs I + + + - - IU - + - - 7

5 35 M RA 46,XY +3 yrs C + + + EN,AN NA - - + - NA 7

6 36 F RAEB 47,XX,+8 -9 yrs I + + - EN NA - - - - + 8

7 39 M RA 47,XY,+8 -1 yr I + + - - NA IU - + - NA 9

8 41 F RA 49,XX,+8,+9,+22 0 I + + - EN NA IU + - - - 6

9 41 F RARS 47,XX,+8 0 I + + - AN NA IU - - - + 7

10 45 F RARS 48,XX,+8,+15 0 I + + - EN,AN - - - 7

11 50 F RA 46,XX,-8,-20,+der(8) -11 yrs I + + - - + IU - + - - 10

t(8;20)(p23;p10), +der(8)t(8;20) (p23;q10)Ħ30ħ

12 52 M RA 47,XY,+22,t(9;22) +4 yrs S + - - EN NA - - + - NA 7

(q34;q11)

13 54 F RA 47,XX,+8 +1 yr I + + - EN + - - - - NA 5

14 56 M RAEB NA 0 S + + - - NA IU,EU - - - NA 7

15 57 M RARS NA +11 mos I + + - EN + IU - - - + 7

16 57 M RA 47,XY,+8 +6 mos I + + - + NA IU - - - NA 7

17 59 M RAEB-t 43,XY,-5,-7,+8,-16, +4 mos I + - + - NA - + + + NA 7

-18,-20, 3q-,7q+,12p-, +2mar

18 72 M RA 47,XY,+8,del(20)(q11) +1.6 yrs I + + - AN NA - - - - + 7

19 74 F RA 45,X,-X,+i(5)(p10),i(7) 0 S + - - - - IU + - - - 11

(q10),+del(7)(q21.2 q32), +del(7)(q21.2 q32),+8, -9,+13, -17,-20,-22,+mar

20^*49 F CMMoL 47,XX,+8 -6 yrs I + + - - + IU + + + -

* Case 20ࠎώ͛ٙಡӘঽּ

a MDSֲ̝ݭĈֶ FAB classification, ³RA: refractory anemia, RARS: refractory anemia with ringed sideroblasts, RAEB: refractory anemia with excess blasts, RAEB-t: refractory anemia with excess blasts in transformation, CMMoL: chronic myelomonocytic leukemia

bϨ๫ͩঽ࠹၆ٺ MDS ۞ॡมĈ“+Ň޽Ϩ๫ͩঽ൴ঽٺ MDS ̝ޢĂ“-Ň޽Ϩ๫ͩঽ൴ঽٺ MDS ̝݈Ă“0Ň޽Ϩ๫ͩঽᄃ

MDSࡗТॡ൴ঽ

c Ϩ๫ͩঽ̶ݭĈֶፂ Beh et's Disease Research Committee of Japan ٺ 2003 ѐޙᛉ۞࣒ࢎޢϨ๫ͩঽ෧ᕝᇾ໤²¹, C: complete type, I: incomplete type, S: suspected type

ᒺᆷĈ MDS, myelodysplasic syndrome; EN, erythema nodosum; AN, acneiform nodules; IU, intestinal ulcers; EU, esophageal ulcers;

NA, not available

(5)

ܑ˟ĈЪ׀֓ͩা̝੻ល൴ֈ̙։া࣏ཏᄃࣧ൴ّ੻ល൴ֈ̙։া࣏ཏֲ̝ݭ̶ҶᄃߖҒវள૱۞ͧྵ

֓ͩা ࣧ൴ّ੻ល൴ֈ̙։া࣏ཏ

Ъ׀੻ល ઼̚ ͟ώ ͟ώ ᔹ઼ ᔹ઼ ͐Ҙ ઼࡚ к઼

൴ֈ̙։ Chen, Matsushima, Toyama, Lee, Lee, De Souza, Jacobs, Greenburg,

া࣏ཏ 2005 2003 1993 2003 2002 1997 1986 1997

ણ҂͛ᚥ ώ͛ 13 14 15 16 17 18 19 20

ঽּᇴ 20 508 288 401 227 205 50 49 816

ѐ᛬̚Ҝᇴ (໐) 47 49 69 NA 57 49 50 62 69

MDSֲݭ̶Ҷ

RA 60.0% 43.9% 31.9% 46.6% 36.1% 36.5% 56% 28.6% 36.0%

RARS 15.0% 2.8% 5.2% 4.0% 8.4% 4.4% 8% 16.3% 15.3%

RAEB 15.0% 27.0% 32.6% 26.7% 39.6% 31.2% 20% 18.4% 25.5%

RAEB-t 5.0% 21.1% 21.5% 16.5% 11.9% 18.5% 8% 10.2% 7.5%

CMMoL 5.0% 5.2% 8.7% 6.2% 4.0% 6.8% 8% 20.4% 15.4%

Unclassified - - - 2.4% - 6.1% 0.2%

ѣߖҒវ̶ژˠᇴ 18 367 264 401 119 205 50 49 816

ϒ૱ߖҒវˠᇴ (%) 1 (5.6%) 231 (62.9%) 124 (47%) 201 (50.1%) 67 (56.3%) 113 (55.2%) 34 (68%) 30 (61.2%) 489 (60%) ள૱ߖҒវˠᇴ (%) 17 (94.4%) 136 (37.1%) 140 (53%) 200 (49.9%) 52 (43.7%) 92 (44.8%) 16 (32%) 19 (38.8%) 327 (40%) ߖҒវள૱̶ҶҫѣߖҒវ̶ژˠᇴѺ̶ͧ

-5/5q- only 0.0% 0.5% 1.5% 2.0% 1.7% 0.9% 10% 2.0% 6%

+8 only 50.0% 4.3% 6.8% 3.7% 5.9% 5.1% 4% 10.2% 5%

-7/7q- only 0.0% 0.3% 7.2% 2.2% 1.7% 1.4% 6% 2.0% 1%

-20/20q- only 0.0% 3.0% 1.5% 4.0% NA NA 2% 2.0% 2%

-Y only 0.0% NA 2.3% 2.2% 2.5% 1.8% 2% 0% 2%

misc single

aberration^* 5.6% 8.5% 4.5% 22.7%^# NA 24.9%^# 0% 8.2% 9%

double aberrations 16.7% 6.0% 6.4% 9.2% NA 6.8% 4% 10.2% 5%

complex aberrations 22.2% 14.4% 22.7% 18.0% 15.1% 13.2% 4% 4.1% 10%

* ੵ -5/5q-, -7/7q-, +8, -20/20q-, -Y ̝γ۞ಏ˘ߖҒវள૱

# ൑ଵੵ -5/5q-, -7/7q-, +8, -20/20q-, -Y ̝ಏ˘ߖҒវள૱

ᒺᆷĈ MDS, myelodysplasic syndrome; RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; RAEB, refractory anemia with excess blasts; RAEB-t, refractory anemia with excess blasts in transformation; CMMoL, chronic myelomonocytic leukemia

ٙϡ۞̶ᙷڱ̙ТϺΞਕֹЧᙷݭּ̝ͧѣ̙ٙ

ТĄԧࣇ૟఺ֱଈ۰ٺЧጡء۞ܑன׶࿅Ν੫၆

֓ͩাଈ۰۞ࡁտͧྵ ( ܑˬ )22-23, 25-29

Ă൴னᄃϏ Ъ׀੻ល൴ֈ̙։া࣏ཏ۞ଈ۰࠹ͧĂЪ׀੻ល

൴ֈ̙։া࣏ཏ۞֓ͩাଈ۰̚བٕࢴ྽ሚႹ۞

஽Җதྵ੼ ( 65% vs 3-36% )Ăҭீঽត۞஽Җத

ྵҲ ( 15% vs 21-75% )Ăᔵ൒А݈അಡӘ࿅ HLA- B51ᄃ֓ͩা۞ޢཬ෈ቯۆѣᙯ²Ăҭдѩѣீ

ঽត۞ˬҜଈ۰่̚ѣ˘Ҝഅତצ HLA-B51 ۞ ᑭߤͷӔౚّĂ߇൑ڱ૟ᓜԖܑன̙Тᕩ׼ٺ

HLA-B51Ă˭ࢬົՀซ˘Վ੅ኢѩᓜԖܑன۞

मளߏӎ׶Ъ׀੻ល൴ֈ̙։া࣏ཏѣᙯĄ

੅ኢ˟ăЪ׀֓ͩাᄃ੻ល൴ֈ̙։া࣏ཏଈ۰

̝ߖҒវ̶ژ

࿅Ν۞ࡁտ൴ன੻ល൴ֈ̙։া࣏ཏଈ۰۞

ᓜԖܑனᄃߖҒវள૱࠹ᙯĂ Greenberg ඈˠ۞

ࡁտ޽΍࿰ޢ։р۞ߖҒវԛёߏϒ૱ă-Y on- lyă del ( 5q ) only ăٕ del ( 20q ) only Ă࿰ޢָ̙

۞ߖҒវΒ߁ complex aberrations ( Тॡѣˬ჌ͽ

˯ߖҒវள૱ ) ٕௐ˛၆ߖҒវள૱Ă׎΁ள૱

(6)

݋࿰ޢ̬ٺ఺׌̂ᙷ̝ม²⁰ĂЯѩԧࣇٕధΞଂ

఺͞ࢬଣ੅఺ֱଈ۰۞ᓜԖܑனߏӎצזߖҒវ ள૱̝ᇆᜩĄܑ˘̚ѣ˟˩ּЪ׀Ϩ๫ͩঽ۞੻

ល൴ֈ̙։া࣏ཏଈ۰̝ߖҒវᑭߤඕڍĂֶፂ IPSS ( International Prognosis Scoring System ) for M D S^{2 0}Ă૟ߖҒវள૱̶ࠎ- 5 / 5 q - o n l y ă + 8 onlyă-7/7q- only ă-20/20q- only ă-Y only ă misc. single aberration ( ੵ˯̣ࢗ჌γ۞ಏ˘ߖҒ វள૱ )ă double aberrations ( Тॡѣ׌჌ߖҒវ ள૱ ) ̈́ complex aberrations ( Тॡѣˬ჌ͽ˯ߖ Ғវள૱ ) ඈˣ჌ᙷݭĂԧࣇ၆ѩ˟˩ҜЪ׀֓

ͩা۞੻ល൴ֈ̙։া࣏ཏଈ۰ᄃ࿅Ν၆ٺࣧ൴

ّ੻ល൴ֈ̙։া࣏ཏଈ۰̝ߖҒវࡁտઇྎႽ

۞ͧྵ ( ܑ˟ )Ă൴ன݈۰۞ߖҒវள૱ּͧྵ

ޢ۰੼΍ࠤк ( 94% vs 32-53% )^13-20ĂࠤҌͧڼᒚ

࠹ᙯّ ( Ѩ൴ّ )੻ល൴ֈ̙։া࣏ཏଈ۰ள૱

ּͧ 80% Հ੼³⁰ĄѩγĂԧࣇ൴னд˩ˣҜѣߖ ҒវᑭߤಡӘ۞ଈ۰̚ѣ˩αּ ( 77.8% ) ׍ѣ trisomy 8Ăͷѣ˝ּ ( 50% ) ่ѣ trisomy 8 ۞ள

૱Ă҃ࣧ൴ّ੻ល൴ֈ̙։া࣏ཏଈ۰Ϊѣ 6.5- 16.3%׍ѣ trisomy 8 Ăд 3.7-10.2% ۞ଈ۰̚ trisomy 8 ߏ઱˘۞ள૱^13-20Ă׌۰̝ม࠹मࠤкĂ

׎ࣧЯࠎңĉ Takeuchi ඈˠࡁտ֓ͩাଈ۰۞୽

͐஧ĂΪдߙֱͽ colchicine ٕԩᒛᘽۏڼᒚ۞

ଈ۰̚൴ன dicentric ې୽͐஧̈́˘ֱߖҒវள૱

( ҭܧߖҒវᇴϫள૱ )³¹Ăд఺˟˩࣎Ъ׀֓ͩ

াᄃ੻ល൴ֈ̙։া࣏ཏ۞ଈ۰̚Ă଀ז੻ល൴ ֈ̙։া࣏ཏ݈Ϊѣ Case 6 അڇϡ colchicine ֽ ڼᒚ֓ͩাĂ׎΁ଈ۰۞੻ល൴ֈ̙։া࣏ཏ݋

̙ΞਕߏЯࠎԩᒛᘽۏٕ chochicine ͔ٙ੓ĄϤ ѩ੅ኢΞۢĂ੼ͧத۞ߖҒវள૱̙֭ਕಏ৷ᕩ Яٺ֓ͩাٕ੻ល൴ֈ̙։া࣏ཏĂԧࣇଯീ

trisomy 8Ξਕᄃ఺ֱଈ۰Тॡ଀ז੻ល൴ֈ̙։

া࣏ཏ̈́֓ͩাѣᙯĄ

੅ኢˬă Trisomy 8 дЪ׀֓ͩা̈́੻ល൴ֈ̙

։া࣏ཏ۞ଈ۰វ̰տౣԷႊ̦ᆃ֎Ғĉ Ϥܑ˘Ξͽۢ྽ĂЪ׀֓ͩাᄃ੻ល൴ֈ̙

։া࣏ཏ۞ଈ۰̚ѣ˩ˬּഅѣབٕࢴ྽ሚႹ۞

ܑனĂ˩˘ּઇ࿅ߖҒវᑭߤ۞ଈ۰̚ѣ˝ּ

( 81.8% ) ׍ѣ trisomy 8 Ăд˛ּ ( 63.6% ) ̚ trisomy 8ߏ่ѣ۞ߖҒវள૱ĂΩѣ˘ּ׍ѣܧ trisomy 8۞ௐˣ၆ߖҒវள૱Ă˘ּ݋ࠎං͌۞

ring 6Ă൒҃д൑བٕࢴ྽ሚႹ۞˛Ҝଈ۰̚Ă ѣּ̣ ( 71.4% ) ૲ѣ trisomy 8 ۞ள૱Ăд׌ּ

( 28.6% ) ̚ trisomy 8 ߏ઱˘۞ߖҒវள૱ĄΩ γĂαּ׀൴ҕგঽត ( Βӣ large vessel vasculi-

ܑˬĈ֓ͩাЪ׀੻ល൴ֈ̙։া࣏ཏᄃ֓ͩাଈ۰̝ᓜԖܑனͧྵ

֓ͩা ֓ͩা

Ъ׀੻ល ᔹ઼ ᔹ઼ ˿҅׎ ᇇ઼ ԓᘷ ͟ώ ઼̚

൴ֈ̙։ Bang, Bang, Gurler, Zouboulis, Kaklamani, Nakae, Dong,

া࣏ཏ 2001 1997 1997 1997 1998 1993 1991

ણ҂͛ᚥ ώ͛ 22 23 25 26 27 28 29

ঽּᇴ 20 1527 1155 2147 196 64 331 98

˾ටሚႹ 100.0^a 98.8 97.5 100.0 99.0 100 98.2 100.0

Ϡത྽ሚႹ 80.0 83.2 56.7 88.2 74.5 78 73.2 81.6

ீొঽត 15.0 50.9 28.5 28.9 58.9 75 69.1 21.4

ϩቲঽត 65.0 84.3 60.6 NA 75.5 94 97.1 NA

੫וྏរวّ 57.1 15.4 NA 56.8 51.8 30 43.8 62.2

ᙯ༼ۆ 35.0 38.4 24.2 15.9 59.0 48 56.9 30.6

ࡤབ྽ঽត 65.0 7.3 4.0 2.8 15.8 3 15.5 35.7

ৠགྷঽត 10.0 4.6 5.7 2.2 12.8 20 11.0 9.2

ҕგঽត 20.0 1.8 NA 16.8 25.1 8 8.9 16.3

HLA-B51วّ 30.8 NA NA NA 56.3 (HLA-B5) NA 55 NA

a ѩ᛼ᇴࣃӮͽѺ̶ܑͧϯ

ᒺᆷĈ NA, not available

(7)

tisᄃ thrombosis ) ۞ଈ۰Ӯѣ trisomy 8 Ă҃˩α

ּϏ׀൴ҕგঽតͷѣߖҒវᑭߤ۞ଈ۰݋Ϊѣ

˩ּ૲ѣ trisomy 8 ( 71.4% )Ąԧࣇ൴ன˘࣎ᔌ ๕Ăдѣབٕࢴ྽ሚႹ̈́ҕგঽត۞ଈ۰Ăྵ൑

఺ֱېڶ۞ଈ۰ѣՀ੼۞ּͧ׍ѣ trisomy 8 ̝ߖ Ғវள૱Ăѩᄃ࿅Ν۞ࡁտ࠹௑^{6 , 11}ĂᔵϏ྿ព

඾मளĂҭΞਕߏঽּᇴϫ͉͌۞ᙯܼĄ

੅ኢαă੻ល൴ֈ̙։া࣏ཏᄃ֓ͩা۞ঽந፟

ᖼ׶Һࠪε૱ă௟ࡪࣟ˸̈́ௐˣ၆ߖҒវ۞ᙯܼ

ܕѐֽѣ෸ֽ෸к۞ᙋፂពϯ੻ល൴ֈ̙։

া࣏ཏ˜ЯҺࠪε૱ጱ࡭੻ល਽ა͔҃੓Ă࿅ޘ

۞௟ࡪᆧϠҡᐌ࿅ޘ۞௟ࡪࣟ˸ ( apoptosis ) Ξྋ ᛖңͽଈ۰۞੻ល̚௟ࡪᇴ఼૱ߏϒ૱ٕᆧΐĂ ҭ׹ᙝҕ୵௟ࡪᇴݒߏഴ͌۞^{3 2}Ą Raza ඈˠࡁ տ੻ល൴ֈ̙։া࣏ཏଈ۰੻ល௟ࡪ̰۞௟ࡪฉ ഇજ˧ጯĂ൴னࡗѣˬ̶̝˘۞௟ࡪ఍ٺЪј DNA۞ېၗĂͽ ISEL ( in situ end labeling ) ԫఙ ઍീĂΒ߁ౄҕ௟ࡪᄃል௟ࡪӮѣ࿅ޘ۞௟ࡪࣟ

˸ன෪³³ć Hellstrom-Lindberg ඈˠֹϡ TUNEL ( nick-end labeling ) ͞ڱĂ൴ன੻ល൴ֈ̙։া࣏

ཏଈ۰̝੻ល̚ϒдࣟ˸۞௟ࡪͧத۞ቁྵϒ૱

ˠ੼ ( 56.3% Ų 3.8% vs 16.2 Ų 1.4%, p=0.0001 )³⁴ć ѩγĂ Gersuk ඈˠ൴னᄃ௟ࡪࣟ˸࠹ᙯ۞ Fas ᄃ Fas-L̝ mRNA д੻ល൴ֈ̙։া࣏ཏଈ۰۞੻

ល̰ CD34+ ௟ࡪܑனྵϒ૱ˠ੼Ăͷົܳซ௟

ࡪܑன Fas ۞ TNF-ɗ׎ mRNA дଈ۰۞੻ល̚

˵ྵϒ૱ˠ੼³⁵ĄܕֽĂ Soland ඈˠ۞ࡁտᙋ၁

˞੻ល̰ࣟ˸ᄃܑன Fas ۞ CD34+ ௟ࡪᇴϫᆧΐ

۞ன෪Ϊ֍ٺѣ trisomy 8 ̝ߖҒវள૱۞ଈ۰Ă д monosomy 7 ۞ଈ۰̚׎၁ߏࢫҲ۞Ăӈֹд Тଈ۰̚Ă׍ trisomy 8 ۞௟ࡪ˵Ξീ଀ͧϒ૱௟

ࡪѣྵ੼۞ Fas ̈́߿̼۞ caspase-3³⁶ĄტЪͽ˯

۞ࡁտ൴னĂΞଯീ࿅ޘ۞ Fas-mediated apopto- s i sд੻ល൴ֈ̙։া࣏ཏଈ۰੻ល਽ა۞፟ᖼ

˯Ξਕҫѣߙ჌ࢦࢋ֎ҒĂ͍׎ߏ૲ѣ trisomy 8

̝ߖҒវள૱۞ଈ۰ćѩ჌࿅ޘ۞௟ࡪࣟ˸่̙

׶ౄҕ௟ࡪώ֗৿ౝѣᙯĂᄃள૱۞੻លᒖဩϺ ѣᙯܼĂ੻លᒖဩ͹ࢋϤҺࠪ௟ࡪ ( ͽ T ௟ࡪࠎ

͹ ) ౅࿅௟ࡪ፬৵ֽአ༼Ă T ௟ࡪ˵ົԽᑝౄҕ

௟ࡪ³²Ă఺ᄲځ˞ T ௟ࡪᄃ੻ល൴ֈ̙։া࣏ཏ ଈ۰۞੻ល਽ა˵ѣࢦࢋᙯܼĄ

Ω˘͞ࢬĂ੻ល൴ֈ̙։া࣏ཏଈ۰˵૱ѣ ҋវҺ়ࠪঽ۞ܑᇈĂॲፂ௚ࢍĂ૲ѣҋវҺࠪ

ܑᇈ۞੻ល൴ֈ̙։া࣏ཏଈ۰ּͧࡗࠎ 1 0 -

19%^32,37Ă˘ี੫၆ 70 Ҝ੻ល൴ֈ̙։া࣏ཏଈ

۰۞ࡁտ൴னĂ੠ᖸαѐ̝ޢĂѣ 13 Ҝ ( 18.6% )

൴ण΍ҋវҺࠪ۞ன෪Ă׎̚ͽ vasculitic over- lap syndrome with leucocytoclastic vasculitisܑனѣ

̱ˠĂѣ׌ˠ൴णࠎ systemic vasculitis Ă൒֭҃

՟ѣ൴னপঅ۞ߖҒវள૱ٕ੻ល൴ֈ̙։া࣏

ཏֲ̝ݭᄃҋវҺࠪ۞ܑன࠹ᙯ³⁷ĄΞਕ۞፟ט Β߁Ĉ੻ល൴ֈ̙։া࣏ཏጱ࡭̙ϒ૱۞ԩࣧ೩ Ӕ ( antigen presenting )ă T ௟ࡪ၆ԩࣧ೩Ӕ۞̙

ϒ૱ͅᑕăٕ B ௟ࡪᄃ T ௟ࡪ̝Ϲ̢үϡள૱Ă ጱ࡭Һࠪ፟ਕ۞৴ใ͔҃੓ҋវҺܑࠪᇈĂ߇ҋ វҺܑࠪᇈΞਕߏ੻ល൴ֈ̙։া࣏ཏ۞ઘᒛা

࣏ཏ ( paraneoplastic syndrome )ćΩѣ˘ࠁᄲڱߏ ѣ˘ВТᛈ൴Я̄ ( trigger ) ৔ᗼ myeloid ̈́ lym- phoidĂඕڍጱ࡭੻ល൴ֈ̙։া࣏ཏ̈́ҋវҺ

ࠪ۞൴Ϡ³⁸Ą

Ҍٺ֓ͩা۞࡭ঽ፟ᖼϫ݈˵̙˩̶୻຾Ă ҭࡁտ൴னᔵ൒ଈ۰វ̰Ϗజ߿̼۞ T ௟ࡪ̝

Fasᄃ Fas-L mRNA ณߏ̿੼۞Ăҭజ߿̼۞ T

௟ࡪ၆ spontaneous ٕ Fas-mediated apoptosis ݒѣ ԩّĂͷ̂ณܑன a n t i - a p o p t o t i c f a c t o r т cFLIPă Bcl-x^Lă NF-ɠB^39-40ĄΩѣᙋፂពϯ߿

ّഇঽˠ̝๝ّ̚஧ᄃҋវҕ୻ૈዳ 18 ̈ॡޢ யϠ̂ณ۞ G-CSF ( granulocyte-colony-stimulating factor ) ֭ѣ apoptosis ഴ͌۞ன෪⁴¹Ăᔘѣࡁ տ ൴ ன ๝ ̚ ّ ஧ Α ਕ ࿅ ੼ ۞ ன ෪ Ă т Ĉ ࿅ ޘ chemotaxisă superoxide Ъј࿅кă IL-6 ă IL- 8ă TNF ɗඈ൴ۆۏኳயϠ࿅к^42-43Ą

ͧྵ֓ͩাᄃ੻ល൴ֈ̙։া࣏ཏ۞࡭ঽ፟

ᖼĂ൴ன׌۰Ξਕ࠰ᄃ apoptosis Αਕள૱ă̙

ϒ૱۞Ϩҕ஧Αਕᄃ௟ࡪ፬৵̶کѣᙯĂ˘ֱҜ ٺௐˣ၆ߖҒវ۞ૄЯΞਕᄃѩѣᙯĂт I L - 7

۞ૄЯҜٺ chromosome 8q12-13⁴⁴Ăབ྽ܑϩ௟

ࡪΞᄦౄ IL-7 Ăߏᕆቯ୽͐஧ܑࢬ IL-7 receptor ( IL-7R ) ۞አ༼Я̄Ă҃ѣࡁտ൴ன IL-7 ᖼങဂ

൴ण΍ᄃˠᙷሚႹّ̂བۆ௡ᖐጯ࠹Ҭ۞ާăၙ

ّඕབۆ⁴⁵Ą˫т TRAIL-R1 ( TNF-related apoptosis-inducing ligand-receptor 1 ) ׶ TRAIL-R2 ( T-

(8)

NF-related apoptosis-inducing ligand-receptor 2 ) ߏ TRAIL ( TNF-related apoptosis-inducing ligand ) ۞ צវĂӮᛳٺ TNFR superfamily Ă׎ૄЯҜٺ 8p21-22Ă TRAIL/TRAIL-R ր௚дአ༼௟ࡪࣟ˸

͍׎ߏ୽͐஧ޮؠّҫѣࢦࢋ֎Ғ⁴⁶Ăᄃ֓ͩা

̈́੻ល൴ֈ̙։া࣏ཏΞਕౌѣᙯܼĄѩγĂ C-mycߏҜٺ 8q24 ۞˘࣎࡭ᒛૄЯĂд੻ល൴ ֈ̙։া࣏ཏ۞࡭ঽ፟ᖼ˯ΞਕԷႊߙ჌֎Ғ⁴⁷Ą

౵ޢĂт݈ࢗٙ੅ኢ࿅۞Ă੻ល൴ֈ̙։া࣏ཏ ଈ۰૱ѣ˘ֱᙷҬઘᒛা࣏ཏ۞ҋវҺܑࠪᇈ΍

னĂ၆ٺЪ׀֓ͩাᄃ੻ល൴ֈ̙։া࣏ཏ۞ଈ ۰ֽᄲĂ֓ͩাΞਕߏ੻ល൴ֈ̙։া࣏ཏ۞ઘ ᒛা࣏ཏ۞ܑᇈ̝˘Ą

ඕኢ

Ъ׀֓ͩাᄃ੻ល൴ֈ̙։া࣏ཏߏܧ૱ց

֍۞ېڶĂЯЪ׀ѩ׌჌়ঽ۞ଈ۰ѣޝ੼ּͧ

૲ѣ trisomy 8 ̝ߖҒវள૱Ă߇ଯീ trisomy 8 Ξ ਕֹѩ׌჌়ঽྵटٽ൴ঽٺТଈ۰֗˯Ąಶᓜ ԖܑனֽᄲĂ఺ֱଈ۰ྵкܑன΍བٕࢴ྽ሚ ႹĂҭྵ͌ீొঽតćѩγĂЪ׀བٕࢴ྽ሚ Ⴙăҕგঽត۞ଈ۰ͧ൑Ъ׀఺ֱܑன۞ଈ۰ѣ

ྵ੼ּͧ૲ѣ trisomy 8 ۞ߖҒវள૱ĂᔵϏ྿ព

඾मளĂҭѣ˘ᔌ๕хдĂଯീ trisomy 8 Ξਕᄃ ଈ۰۞֓ͩাܑன࠹ᙯĄᙯٺѩ˟჌়ঽ۞൴ঽ

፟ᖼᄃ࠹ᙯّ̪ޞՀк۞ࡁտֽଣ੅Ą

ણ҂͛ᚥ

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3.Bennett JM, Catovsky D, Daniel MT, et al. The French- American-British (FAB) Co-operative Group. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189-99.

4.Yamato K. Successful cord blood stem cell transplantation for myelodysplastic syndrome with Beh et's disease. Int J Hematol 2003; 77: 82-5.

5.Yano K, Eguchi K, Migita K, et al. Beh et's disease complicat- ed with myelodysplastic syndrome. A report of two cases and review of the literature. Clin Rheumatol 1996; 15: 91-3.

6.Ogawa H, Kuroda T, Inada M, et al. Intestinal Beh et's disease associated with myelodysplastic syndrome with chromosomal

trisomy 8-a report of two cases and a review of the literature.

Hepato-Gastroenterol 2001; 48: 416-20.

7.Ohno E, Ohtsuka E, Watanabe K, et al. Beh et's disease associated with myelodysplastic syndromes. Cancer 1997; 79: 262- 8.

8.Tomonari A, Tojo A, Takahashi T, et al. Resolution of Beh et's disease after HLA-mismatched unrelated cord blood transplantation for myelodysplastic syndrome. Ann Hematol 2004; 83:

464-6.

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A Case Report and Literature Survey on Beh et's Disease with Myelodysplastic Syndrome

Yi-Chun Lin, Toong Hua Liang¹, Wei-Sheng Chen², and Hsiao-Yi Lin³

Beh et's disease (BD) is a systemic inflammatory disease of unknown etiology. The main pathology is vasculitis. Myelodysplastic disease (MDS), a heterogeneous group of clonal hematologic disorders, is classified in- to five subtypes. Normo- or hypercellularity with dysplasia of bone marrow and peripheral cytopenia of at least one lineage are noted in all subtypes, except chronic myelomonocytic leukemia (CMMoL) subtype, which is char- acterized by peripheral monocytosis. There were rare cases with coexistent BD and MDS. The majority belonged to incomplete types of Beh et's disease and the refractory anemia subtype of MDS. Here we present a case of 49-year-old woman with Beh et's disease initially who were diagnosed with MDS six years later. This is the first report of a case of BD associated with the CMMoL subtype of MDS. The chromosome karyotype was 47XX and trisomy 8. After reviewing the past literatures, totally twenty cases with this patient included have concomitant BD and MDS. The temporal sequence of onset is not constant. Comparing their clinical manifestations with the pre- vious case studies, we found they have higher percentages of intestinal/esophageal ulcers than those of BD without MDS (65% vs 3-36%), whereas less percentages of eye lesions (15% vs 21-75%). Besides, the chromosomal analysis revealed that trisomy 8 is more prevalent in those of MDS with BD than MDS without BD (77.8% vs 6.5-16.3%). In these twenty cases with BD and MDS, trisomy 8 is more common in patients with intestinal/e- sophageal ulcers and vascular lesions (large vessel vasculitis or thrombosis) than those without (81.8% vs 71.4%, 100% vs 71.4% individually). Besides, trisomy 8 is the single chromosome aberration in more patients with intestinal/esophageal ulcers than those without (63.6% vs 28.6%). Although it is not significant, we note a tenden- cy that patients with concurrent MDS and BD have more intestinal/esophageal ulcers and vascular lesions if they carry trisomy 8. From this case review, we make a conclusion: although diagnosis of BD is mainly based on disease history, physical examination and laboratory tests, it is equivocal for some patients. In this condition, a myelodysplastic patient with trisomy 8 warns the possibility of coexistent BD, especially the intestinal or vascular manifestations. ( J Intern Med Taiwan 2008; 19: 175- 184 )

Department of Internal Medicine, Taipei City Hospital;

1

Section of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Municipal WanFang Hospital;

2

Section of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital;

3