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Resolution of atopic dermatitis following allogeneic bone marrow transplantation for chronic myelogenous leukemia

Bone Marrow Transplantation volume 35, pages 12231224 (2005) | Download Citation

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Atopic dermatitis is a complex, multifactorial, cutaneous manifestation of the atopic diathesis.1 A wide range of cell-mediated immune defects associated with T-lymphocytes have been reported in atopic dermatitis.2 Recently, some patients with coincidental autoimmune disease who underwent allogeneic bone marrow transplantation (BMT) for a malignancy have been cured of their autoimmune disease.3, 4, 5, 6 We describe a patient with chronic myelogenous leukemia (CML) whose atopic dermatitis resolved completely over a 4-year follow-up period, after allogeneic BMT.

A 33-year-old man with CML was transferred to our hospital in October 2000 for BMT. He had been treated with interferon-α and hydroxyurea for 2 years, but there was no cytogenetic response. He had suffered from atopic dermatitis for 20 years and had been treated with topical corticosteroids. His skin lesions were moderate and constant, and he had no respiratory problems. He underwent an allogeneic BMT with marrow donated from an unrelated HLA-identical woman, in November 2000. The donor had no medical history of atopy. Pre-transplant conditioning consisted of thiotepa (days −8 and −7; 200 mg/m2/day), cyclophosphamide (days −6 and −5; 2250 mg/m2/day), and fractionated total body irradiation (days −4 to −1; 3 Gy/day). He received graft-versus-host disease (GVHD) prophylaxis with methotrexate (day 1, 10 mg/m2/day; and days 3, 6, and 11, 6 mg/m2/day) and tacrolimus (0.03 mg/kg/day) as a continuous infusion. He also received 300 μg/day granulocyte colony-stimulating factor by continuous infusion, beginning on day 1, to aid granulocyte recovery. Bone marrow engraftment was successful, and complete chimerism was confirmed by fluorescence in situ hybridization analysis using X- and Y-chromosome probes. He complained of painful palmoplantar erythema on day 11. This was confirmed as acute GVHD (grade I) by skin biopsy. Treatment with prednisolone was begun on day 35 to relieve the pain, although the skin lesion was limited. On day 65 after BMT, he developed Epstein–Barr viral meningitis, but this resolved with discontinuation of tacrolimus and administration of an antiviral agent and immunoglobulin. Furthermore, he developed bronchiolitis obliterans organizing pneumonia 4 months after BMT. His atopic dermatitis resolved around day 70 post transplant. His serum IgE level was 3130 mg/dl pre-transplant and this decreased to 212 mg/dl on day 125. His CML remains in remission and he has been free of atopic dermatitis for 4 years post transplant, despite discontinuation of immunosuppressive treatment.

During allogeneic BMT, the immune system of the host is effectively eliminated by the pre-conditioning regimen, and immunity after BMT is mostly of donor origin. Thus, it is likely that the course of autoimmune disorders can be modified by allogeneic BMT.7 Atopic dermatitis is thought to be an autoimmune or allergic disease, as indicated by increasing evidence for the role of a cellular immune reaction in the pathogenesis.1, 2 In the present case, the immunosuppressive treatment used to prevent GVHD may have also influenced the clinical course of the atopic dermatitis. However, it is unlikely that the long-lasting remission could be attributed to the tacrolimus given for 4 months after BMT, because recurrence of atopic dermatitis after discontinuation of tacrolimus is common. By contrast, transfer of atopy following BMT has been observed in several case reports.8, 9 It is of particular note that allergen-specific IgE-mediated hypersensitivity may be adoptively transferred by BMT from an atopic donor to the recipient.8 Additionally, experimental studies in animal models have demonstrated that various autoimmune diseases can be transferred to healthy animals by BMT.10 Taking these findings together, ablation of the host hematopoietic system and reconstitution with the donor immune system resolved the atopic dermatitis in this patient. Allogeneic BMT is not generally considered for treatment of autoimmune disease because of its significant associated mortality and morbidity. However, we recommend that such patients be reported to allow accumulation of information, which will lead to an understanding of the mechanism of immune reconstitution after allogeneic BMT.

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  1. Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    • H Koharazawa
    • , H Kanamori
    • , M Takabayashi
    • , S Yamaji
    • , J Taguchi
    • , K Fujimaki
    •  & Y Ishigatsubo

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https://doi.org/10.1038/sj.bmt.1704990

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