A 41-year-old woman with myelodysplastic syndrome underwent unrelated bone marrow transplantation following conditioning with fludarabine, busulfan, total body irradiation, and anti-thymocyte globulin. She received tacrolimus and short-term methotrexate for graft-versus-host disease (GVHD) prophylaxis. After engraftment, she developed acute GVHD involving the skin, gut, and liver. Even after treatment with glucocorticoids, human mesenchymal stem cells, and ruxolitinib, skin GVHD progressed and caused extensive epidermolysis and erosions with persistent bleeding. The patient was started on a daily skin care regimen, which included washing, application of dimethyl isopropylazulene and betamethasone ointment, and topical trafermin and hydrogel wound dressing for bleeding sites. A multi-disciplinary team consisting of hematologists, plastic surgeons, and nurses, and physical therapists, psychiatrists/clinical psychologists, and palliative care providers for physical, mental, and pain supportive care managed the patient's care. After 4 months of treatment under this team, complete epithelial regeneration was achieved. This case demonstrates the efficacy of local skin care and multi-disciplinary collaboration in acute GHVD causing extensive skin damage.