Effective and less invasive diagnostic strategy for gastrointestinal GVHD

Abstract

Background and study aims: Rectosigmoidoscopy with biopsy has been regarded to be a useful procedure to diagnose gastrointestinal graft-versus-host disease (GVHD). However, little is known about the specific colonoscopic features of gastrointestinal GVHD. In this study, we focused on the 4 unique colonoscopic findings - orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect - which are possible specific findings of gastrointestinal GVHD. We aimed to estimate the usefulness of these four unique colonoscopic findings in the rectosigmoid portion to diagnose gastrointestinal GVHD.

Patients and methods: Seventy patients who were histologically diagnosed with gastrointestinal GVHD at our institute were retrospectively enrolled. Colonoscopic findings were reviewed, focusing on the four characteristic findings. The percentage of the positive cases for the characteristic findings was calculated. The final scoping portion and the number of cases showing any of the four characteristic findings in the rectosigmoid portion were also evaluated. The relationships between biopsy sites and the histological findings were also evaluated.

Results: Orange peel appearance was observed in 66 cases (94.3 %). Spotty redness was observed in 45 cases (64.3 %). Small mucosal sloughing was observed in 49 cases (70.0 %). Diffuse mucosal defect was observed in six cases (8.6 %). The number of cases that were concurrently positive for one, two, and three findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively. Fifty-eight cases (82.9 %) were investigated up to the rectosigmoid portion, and 12 (17.1 %) were investigated beyond the sigmoid colon. All of the cases showed at least 1 of the 4 characteristics in the rectosigmoid portion. The percentage of crypt apoptosis in the biopsy specimen from orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect were 87.5 %, 83.3 %, 87.2 %, and 88.9 %, respectively.

Conclusion: Orange peel appearance, spotty redness, small mucosal sloughing, and diffuse mucosal defect are the characteristic colonoscopic findings useful for diagnosis of gastrointestinal GVHD. These findings are frequently observed in the rectosigmoid portion. The histological detection rates for crypt cell apoptosis from these findings are high. Identifying the four characteristic findings on rectosigmoidoscopy and taking biopsies from these areas could be essential for the diagnostic strategy for gastrointestinal GVHD.

Fig. 1

Definitions of the 4 characteristic findings. a Orange peel appearance: mucosal edema with granular surface looking like “orange peel” or “tortoiseshell,” which was usually highlighted with indigo carmine dye spraying. b Spotty redness: redness of 1 to 2 cm in diameter with an unclear border. c Small mucosal sloughing: a small superficial area of mucosal sloughing with various types of shapes, with a clear border. d Diffuse mucosal defects: large ulcers with irregular or geographic shapes.

Fig. 2

Flow diagram of the cases. A total of 93 patients with suspicious symptoms of gastrointestinal GVHD after allogenic HSCT received colonoscopic evaluations. Out of all 93 patients, 72 were pathologically diagnosed with gastrointestinal GVHD. Seventy cases with histologically proven gastrointestinal GVHD without CMV infection were finally enrolled in this study. GI GVHD, gastrointestinal graft-vs-host disease; HSCT, hematopoietic stem cell transplantation; CMV, cytomegalovirus

Fig. 3

Percentage and examples of the positive cases with orange peel appearance. Orange peel appearance was observed in 66 of 70 cases (94.3 %).

Fig. 4

Percentage and examples of the positive cases with spotty redness. Spotty redness was observed in 45 of 70 cases (64.3 %).

Fig. 5

Percentage and examples of the positive cases with small mucosal sloughing. Small mucosal sloughing was observed in 49 of 70 cases (70.0 %).

Fig. 6

Percentage and examples of the positive cases with diffuse mucosal defect. Diffuse mucosal defect was observed in 6 of 70 cases (8.6 %).

Fig. 7

Combinations of the 4 characteristic findings. There was only 1 patient who did not have any of the 4 findings. Four of 70 patients (5.2 %) presented with all 4 findings. The number of patients who were concurrently positive for 1, 2, and 3 findings were 16 (20.8 %), 20 (26.0 %), and 34 (48.6 %), respectively.

Fig. 8

The final scoping portion and the number of the cases. Fifty-eight of 70 patients (82.9 %) were investigated with rectosigmoidoscopy. All of these 58 cases presented with at least 1 of the 4 characteristic findings in the rectosigmoid portion. There were 12 patients (17.1 %) in whom colonoscopic observations were performed beyond the sigmoid colon. All of these 12 cases presented with at least 1 of the 4 characteristic findings up to the sigmoid colon.

Fig. 9

Colonoscopic and histological findings of a typical case with orange peel appearance and small mucosal sloughing. The patient was a 51-year-old female with gastrointestinal GVHD. The colonoscopic and histological examinations were performed at Day 42 after CBT for AML. a, b Orange peel appearance and small mucosal sloughing were observed. c, d Magnified endoscopic findings of the small mucosal sloughing. e Histological findings of the biopsy specimen taken from an area with an orange peel appearance. Crypt apoptosis was found. f Histological findings of the biopsy specimen taken from an area of small mucosal sloughing. Destruction of goblet cells was found. gastrointestinal GVHD, gastrointestinal graft-vs-host disease; CBT, cord blood transplantation; AML, acute myeloid leukemia.

Fig. 10

Hypothesis: Sequential transition of colonoscopic findings. The 4 characteristic findings picked up in the current study could appear gradually and successively as the gastrointestinal GVHD proceeds.