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    Home > Active Ingredient News > Antitumor Therapy > Severe rash occurred after cytarabine chemotherapy. Can subsequent chemotherapy continue to be used?

    Severe rash occurred after cytarabine chemotherapy. Can subsequent chemotherapy continue to be used?

    • Last Update: 2021-04-14
    • Source: Internet
    • Author: User
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    Author: This article is the author's permission River Island NMT Medical publish, please do not reprint without authorization.

    Cytarabine is a cell cycle specific drug, often used to treat hematological malignancies, benefiting many patients.

    On the other hand, the use of cytarabine also causes many adverse reactions, such as bone marrow suppression, fever, liver and kidney damage, and skin rash.

    Some patients discontinued the drug due to severe side effects, affecting the patient's next treatment.
    Among them, the skin disease is a common side effect of the patient using cytarabine.
    If the patient has a severe rash due to the use of cytarabine, can the follow-up treatment continue to use? Case data Patient, female, 53 years old, with "dizziness, malaise for 2 months, worsening for 20 days" as the main complaint.
    She was admitted to the Department of Hematology on January 25, 2021.
    Physical examination after admission: body temperature: 36.
    6℃, heart rate 96 beats/ Minutes, breathing 20 times/min, blood pressure 100/70mmHg, clear mind, poor mental response, severe anemia, pale skin and mucous membranes all over the body, no yellowing, rash and bleeding spots, no palpable swelling of superficial lymph nodes all over the body, no sclera Blue band is seen, tongue papillae are not significantly atrophy, pharynx is not congested, liver and spleen are not palpable under ribs.

    01 Auxiliary examination blood routine: white blood cell count: 2.
    15×109/L, hemoglobin: 71g/L, platelet count: 60×109/L Bone marrow: active bone marrow hyperplasia, granular lineage, increased proportion of blast cells, accounting for 3.
    5%, occasionally See Auer body, erythroid hyperplasia, the proportion of mid-to-late young erythrocytes is obviously increased, megaloblasts can be seen, nuclear budding, binuclear and multinucleated erythrocytes can be seen, some of the cells are too large, polychromatic erythrocytes can be seen, and the proportion of monocytes is increased.
    High, mainly immature cells, accounting for 10%, the cell size varies, some cells are too large, the nucleus is twisted, folded, the chromatin is loose and slender, the nucleolus is not obvious, the cytoplasm is rich, and a few small dust-like particles are visible The platelets are scattered, distributed in small clusters, and the number is normal.Immunophenotyping: The gating analysis on the CD45/SSC dot chart shows that the primitive area cells account for about 6% of nuclear cells, and they are concentrated, mainly expressing CD13, CD34, CD117, and some expressing HLA-DR, CD38; monocytes account for about Nucleated cells are 7.
    5%, phenotypic mature; granulocytes occupy about 10.
    5% of nuclear cells, the proportion is significantly reduced, no obvious developmental abnormalities; nucleated red blood cells occupy about 63% of nuclear cells, the proportion is significantly increased, expressing CD58, CD71, GlyA does not express CD36; lymphocytes account for about 13% of nuclear cells, the proportion is reduced, and the distribution of lymphatic subgroups is roughly normal.

    Tip: It can be seen that about 6% of the original myeloid cells are concentrated in the distribution, accompanied by a significantly higher proportion of nuclear red blood cells, positive for the leukemia fusion gene EVI1 gene, chromosome karyotype 46XX, t(3;3)(q21;q26) [6].

    02MDS-EB-2 was diagnosed (IPSS-R score 6 points), and the prognosis was high-risk group.

    03 During the course of treatment, the patient was given (IA (Idarubicin 12mg/m2, d1-3) + 100mg, q12h, d1-d7) on January 27, 2021.
    Itching and discomfort on the back of the hand appeared on the first day after the chemotherapy ended.
    And it gradually progressed to itching and discomfort on the limbs.

    The skin of the extremities appeared scattered in large patches of red rash, slightly protruding from the skin surface, and did not fade under pressure, without obvious ulceration or peeling (see Figure 1 below).

    Figure 1 The skin changes of the lower limbs and the back of the foot were given oral anti-allergic drugs and intravenous infusion of small doses of hormones.
    After 1 week, the patient's rash gradually subsided, and after 2 weeks, the patient's rash basically disappeared.

    What is the cause of the patient’s late-onset severe skin rash? Can cytarabine be used for subsequent chemotherapy? Discussion Cytarabine is an anti-metabolic drug, usually used to treat hematological malignancies, especially acute myeloid leukemia (AML), acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

    Cytarabine is also a cell cycle specific drug that inhibits cell division by inhibiting DNA synthesis in the S phase of the cell cycle.

    Related side effects caused by cytarabine are dose-dependent.
    Common adverse reactions include bone marrow suppression, fever, cerebellar toxicity, cardiomyopathy, liver and kidney insufficiency, necrotizing enterocolitis, pancreatitis, acute respiratory distress, corneal toxicity, Side effects related to skin diseases.

    The main cause of adverse reactions is related to the release of cytokines [1].

    Skin adverse reactions caused by cytarabine are more common, usually manifested as mycelial outbreaks, which mainly occur in the site of the bone, the intertrigeminal zone, or to a lesser extent, the elbows, knees, neck, and ears.

    [2] Cytarabine can cause a variety of skin disease manifestations.
    Common skin reactions include abnormal morphological outbreaks and toxic erythema-manifested as painful erythema or edematous plaques on the tip of the hand and the three-terminal area.
    The frequency of appearance on the elbows, knees, neck and ears is low, [3] can be manifested as erythema and maculopapular rash, erythema on the palm and plantar area with tenderness, severe blisters and desquamation.

    Skin biopsy revealed: vacuolar degeneration of epidermal basal cells, with a small amount of lymphocyte infiltration in the epithelium.

    The typical rash induced by cytarabine usually occurs 6-12 hours after cytarabine use, and can be relieved by stopping the use.

    The incidence of systemic rash caused by cytarabine is about 3%-72%, and it is more common in patients receiving high-dose cytarabine.

    [4] Low-dose cytarabine has also been reported to cause systemic rash in adults and children.

    The multiple skin manifestations of skin toxicity caused by cytarabine may be attributed to genetic polymorphisms involved in drug metabolism.
    They may be related to cell damage to the epidermis, endocrine sweat glands and ducts, which are caused by the direct toxicity of chemotherapy of.

    [5] In addition, hypersensitivity is one of the possible reasons, which may be attributed to the skin toxicity of cytarabine.

    [6] Most of the adverse skin reactions caused by cytarabine are delayed-type hypersensitivity reactions that occur 1-2 weeks after drug administration.

    [7] Dexamethasone can be routinely used during chemotherapy, and the rash will subside 3-7 days after treatment with anti-allergic drugs, which will not affect the next course of treatment.

    The patient was admitted to the hospital again and was treated with cytarabine chemotherapy again, but there was no manifestation of skin diseases such as rash.

    Severe rash after cytarabine chemotherapy does not affect the use of the next course of treatment, but the patient’s clinical manifestations should be closely monitored during chemotherapy.
    Once related rash manifestations appear, measures must be taken as soon as possible to avoid exfoliative dermatitis and other threats Patient's life.

    References 1.
    Doval Divya,Kumar Sharma Sanjeev,Kumar Meet et al.
    Cytarabine ears-A side effect of cytarabine therapy.
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    J Oncol Pharm Pract, 2020, 26: 471-473.
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    Jaruvijitrattana Pitchaya,Chanprapaph Kumutnart,Bilateral Ear Swelling and Erythema after Chemotherapy: A Case Report of Ara-C Ears.
    [J] .
    Case Rep Dermatol, 2019, 11(2): 226-232.
    3.
    (Bolognia JL, Cooper DL, Glusac EJ.
    Toxic erythema of chemotherapy: a useful clinical term.
    J Am Acad Dermatol.
    2008 Sep;59((3)):524–5294.
    Burgdorf WH, Gilmore WA and Ganick RG.
    Peculiar acral erythema secondary to high-dose chemotherapy for acute myelogenous leukemia.
    Ann Intern Med 1982; 97: 61–62. 5.
    Bolognia JL, Cooper DL, Glusac EJ.
    Toxic erythema of chemotherapy: a useful clinical term.
    J Am Acad Dermatol.
    2008 Sep;59((3)):524–529.
    6.
    Susser WS, Whitaker-Worth DL, Grant-Kels JM.
    Mucocutaneous reactions to chemotherapy.
    J Am Acad Dermatol.
    1999 Mar;40((3)):367–398.
    7.
    Ruben BS, Yu WY, Liu F, Truong SV, Wang KC, Fox LP.
    Generalized benign cutaneous reaction to cytarabine.
    J Am Acad Dermatol.
    2015 Nov;73((5)):821–828.
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