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Severe stomatitis and ileocecal perforation developed after all-trans retinoic acid monotherapy in an HLA-B51-positive patient with acute promyelocytic leukemia.
A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.
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