Cyclophosphamide therapy in Sweet's syndrome complicating refractory Crohn's disease - Efficacy and mechanism of action

Background: Sweet's syndrome is a rare extraintestinal manifestation of Crohn's disease that is usually treated by corticosteroids. Cyclophosphamide therapy has been shown to be effective in steroid-refractory Crohn's disease with extraintestinal manifestations. The mechanism of action remains obscure. Here, we report about a case of steroid-refractory Sweet's syndrome accompanying Crohn's colitis treated by cyclophosphamide. Methods: At baseline and two weeks after initiating cyclophosphamide pulse therapy, clinical symptoms were evaluated and apoptosis in mononuclear cells of the colon mucosa was quantified via immunofluorescence TUNEL-labeling. Ongoing clinical follow-up lasts for more than three years. Results: Cyclophosphamide pulse therapy resulted in complete resolution of luminal activity and extraintestinal manifestations. TUNEL-marked CD4 ⁺, CD8 ⁺ and CD68 ⁺ cells in intestinal biopsies showed a 338% increase as compared to baseline. Conclusions: Cyclophosphamide therapy was highly effective in steroid-refractory Crohn's colitis accompanied by Sweet's syndrome for induction of remission. Furthermore, apoptosis of mononuclear cells in the colon mucosa, including CD68 ⁺ macrophages as well as CD4 ⁺ and CD8 ⁺ cells, appears to be a component of the anti-inflammatory effect of cyclophosphamide in Crohn's disease.