Graft-versus-host diseases characterized by effusion: A case of steroid-refractory graft-versus-host disease

Abstract

Background: Although the biology of steroid-refractory acute GVHD is still unknown, the pathogenesis of steroid-refractory acute GVHD is recognized to be associated with aberrant cytokine milieu. Case presentation: We treated a 41-year-old Japanese male representing a characteristic clinical manifestation among unspecific cases of heterogeneous steroid-refractory acute GVHD. The patient underwent allogeneic bone marrow transplantation due to relapsed neurolymphomatosis. He achieved neutrophil engraftment on day 21 with mild engraftment fever. Acute GVHD occurred on day 56 after transplantation with systemic skin eruptions and precedent body weight gain. Corneal ulceration and gut GVHD symptoms followed the skin lesions sequentially. A biopsy of skin and gut mucosa revealed pathological GVHD. We recognized that the patient presented anasarca symptoms due to acute GVHD. We treated the patient with 1.0 mg/kg corticosteroids (prednisolone) starting on day 68, but his edema worsened. He did not respond to 2.0 mg/kg prednisolone from day 80. He required artificial ventilation on day 80 due to the bilateral massive pleural effusion and died of respiratory failure on day 99 after transplantation. A measurement of serum cytokines before corticosteroid therapy, IL-6 (61.5 pg/mL; normal range: <4.0), VEGF (51 pg/mL; <38.3), IFNγ (0.2 IU/mL; <0.1), and TNF-α (10.5 pg/mL; 0.6–2.8) were elevated. Th2 cytokines, IL-4 (7.2 pg/mL; <6.0) and IL-10 (6.0 pg/mL; <5.0) were also elevated. Conclusions: Our case was prominently characterized by anasarca manifested as follows: systemic edema, massive ascites and pleural effusion. We speculated that acute/chronic GVHD with anasarca has an immunological propensity for proinflammatory and the Th2 cytokine milieu. We advocate that immunological modification by biologic agents such as tocilizumab would be promising theoretically for the treatment of such type of GVHD. Keywords: Graft-versus-host disease, Corticosteroid, Anasarca