azathioprine induced severe bone marrow suppression in autoimmune hepatitis. [case presentation with...
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Autoimmune hepatitis
Azathioprine induced severe bone marrow suppression
천안 충무병원 소화기내과 류기현
206810 이O희 48/F
• C.C.: OT/PT elevation
• P.I.: 외부병원 급성 간염 소견으로 추가 검
사 위해 의뢰 됨.
Initial Blood Examination
• CBC: 4300-11.3-35.2-163K
• PT/PTT: 11.7/27.2
• OT/PT: 586/822, TB/DB: 1.3/1.0, GGT:676
• HBsAg/Anti-HBsAb (-/+), Anti-HCV(-)
Blood Examination
• ANA(+,1:1280), ASMA(+), Anti LKM Ab(-)
• AMA(-)
• IGG: 3415mg/dl(700~1600)
• SPEP: polyclonal gammopathy
• Bridging necrosis with early cirrhotic changes
Biopsy
Impression
• Autoimmune hepatitis
Progress
• 2013-7-2
– Pd(15)+Azt(50) combination therapy start
• 2013-7-9
– Hair loss, sore throat
– ANC: 71.4
Progress
Progress
• G-CSF 약 2주간의 투여 후 백혈구 수치의
호전.
• 혈색소 수치는 약 2개월 후 회복.
Autoimmune hepatitis
• 자가면역질환
– 면역 이상으로 특정 자가세포를 외부세포로 인지하고 공격하여 파괴하는 질환
• Autoimmune hepatitis.
– Unresolving, predominantly periportal hepatitis of unknown etiology.
– Usually with hypergammaglobulinemia and tissue autoantibodies.
– Which is responsive to immunosuppressive therapy.
Dignostic Scoring System
Indications for Treatment
Absolute Relative None
Serum AST≥10 fold ULN Symptoms (fatigue, arthralgia,
jaundice)
Asymptomatic with normal or
near normal serum AST and γ
globulin levels
Serum AST≥5 fold ULN and γ
globulin level≥2 fold ULN
Serum AST and/or c globulin
less than absolute criteria
Inactive cirrhosis or mild portal
inflammation
(portal hepatitis)
Bridging necrosis or multiacinar
necrosis on histological
examination
Interface hepatitis Severe cytopenia (white blood
cell counts <2.5X109/L or
platelet counts <50X109/L)
or known complete deficiency of
TPMT activity precludes
treatment with azathioprine
Incapacitating symptoms Osteopenia, emotional instability,
hypertension, diabetes, or
cytopenia (white blood cell
counts 2.5 109/L
or platelet counts 50 109/L)
Vertebral compression,
psychosis, brittle diabetes,
uncontrolled hypertension,
known intolerances to
prednisone or azathioprine
Immunosuppressive Treatment
Azathioprine-Related Side Effects
hypoxanthine guanine
phosphoribosyl transferase
Interfere with purine nucleotide synthesis within the cell cycle and
impair proliferation of rapidly dividing T and B lymphocytes
Thiopurine
methyltransferase
6-mercaptopurine
6-methyl mercaptopurine
6-thioguanines
Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The
blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease
over 27 years in one hospital. Altogether 739 patients (422 with Crohn's disease, 284 with ulcerative
colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of
12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for
the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was
withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed
symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine
of whom it was severe (white blood count < 2.0 x 10(9)/l). Of these nine patients, three were
pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients
with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet
count < 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in
isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe.
Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years
after starting the drug) and occurred either suddenly or over several months. Bone marrow
suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is
potentially severe. Leucopenia is the commonest and most important haematological complication.
Regular monitoring of the full blood count is recommended during treatment.
Result
Result(1)
Result(2)
감사합니다.
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