PMC8160115_01
Colonoscopic and pathological findings in a patient with intestinal Behcet's disease before the treatment. (A) Colonoscopy revealed punched-out, deep and semi-circumferential ulcers in the cecum (top), and sigmoid colon (bottom), respectively. (B) Colonic biopsy samples were subjected to hematoxylin and eosin (H&E) staining and immunohistochemical analysis to visualize CD3+ T cells, CD68+ macrophages, and myeloperoxidase (MPO)+ granulocytes. Accumulation of immune cells and destruction of crypt architecture were observed in tissues stained by H&E. Colonic mucosa of this patient with intestinal Behcet's disease was characterized by the infiltration of CD3+ T cells, CD68+ macrophages, and MPO+ granulocytes. Scale bar, 100 mum.
fmed-08-679237-g0001.jpg
PMC8160115_01_fmed-08-679237-g0001.jpg
F1
Deep, punched-out, oval-shaped, and semi-circumferential ulcers were observed in the cecum and sigmoid colon, respectively, during colonoscopy (Figure 1A). Pathological examination revealed destruction of the crypt architecture and massive accumulation of lymphocytes and granulocytes in the colonic lamina propria (Figure 1B). As shown in Figure 1B, the colonic mucosa was characterized by massive accumulation of CD3+ T cells, CD68+ macrophages, and MPO+ granulocytes, but not of CD20+ B cells (data not shown).
Colonoscopic findings in a patient with intestinal Behcet's disease after the treatment with prednisolone and infliximab. (A) Clinical course of a patient with intestinal Behcet's disease. Day 0 was defined as on day of admission. (B) Colonoscopy performed after the treatment with prednisolone (PSL, Day 42) revealed semi-circumferential ulcers in the sigmoid colon. Disappearance of multiple ulcers was seen in the sigmoid colon after five times injections of infliximab (IFX, Day 206).
fmed-08-679237-g0002.jpg
PMC8160115_01_fmed-08-679237-g0002.jpg
F2
The patient was then treated with oral PSL (40 mg/day) with a tapering schedule as shown in the clinical course (Figure 2A), which again failed to improve his symptoms. As shown in Figure 2B (top panel), active ulcers were still present in the cecum and sigmoid colon. Five injections of IFX, which was tolerable without adverse events, led to complete remission in this case, as indicated by the complete disappearance of colonic ulcers through colonoscopy, and by improvement of the patient's symptoms (Figure 2B, bottom panel).
Quantitative polymerase chain reaction analyses in colonic biopsy samples. Colonic biopsy samples were subjected to quantitative polymerase chain reaction analyses to determine expression of cytokines and chemokines. Colonic biopsy samples were obtained before the treatment (Day 7 in Figure 2A), after the treatment with prednisolone (PSL, Day 42 in Figure 2A), and after the treatment with infliximab (IFX, Day 98 in Figure 2A). mRNA expression levels of cytokines, chemokines (A), and forkhead box P3 (FOXP3) (B) were normalized by that of beta-actin mRNA.
fmed-08-679237-g0003.jpg
PMC8160115_01_fmed-08-679237-g0003.jpg
F3
The levels of mRNAs encoding proinflammatory cytokines and chemokines were compared in samples isolated before treatment (Day 7), after treatment with PSL (Day 42), and after three injections of IFX (Day 98). qPCR analyses revealed that the colonic mucosa before treatment was characterized by elevated mRNA expression levels of IL-17, IL-23, CXCL9, CXCL10, and IFN-beta (Figure 3A). We also examined the mRNA expression of FOXP3 and found that treatment with IFX markedly increased its levels in the colonic mucosa (Figure 3B).