Table 2

Immune checkpoint inhibitor-associated duodenitis (ICI-Duo) and ICI-associated celiac disease (ICI-CeD) clinical course

CharacteristicsICI-Duo (n=9)ICI-CeD (n=8)P value
Time to symptoms onset (median, days)
 α-CTLA-441.5 (n=4)31.0 (n=1)0.616
 α-PD-(L)1221 (n=3)119 (n=5)0.79
 Combined therapy27.5 (n=2)81 (n=2)0.487
 Overall4882.50.623
Symptoms at diagnosis
 Abdominal pain6/9 (67%)5/8 (62.5%)>0.999
 Diarrhea7/9 (78%)6/8 (75%)>0.999
 Nausea/vomiting5/9 (56%)2/8 (25%)0.314
 Weight loss0/9 (0%)0/8 (0%)>0.999
 BRBPR1/9 (11%)0/8 (0%)>0.999
Extraintestinal manifestations
 Head fog/headaches1/9 (11%)1/8 (12.5%)>0.999
 Fatigue5/9 (56%)2/8 (25%)0.334
 Dermatitis herpitiformis0/9 (0%)0/8 (0%)>0.999
 B12 deficiency*0/2 (0%)1/6 (17%)>0.999
 Vitamin D deficiency0/0 (0%)2/4 (50%)>0.999
 Iron deficiency1/3 (33%)2/4 (50%)>0.999
 Folate deficiency0/2 (0%)0/4 (0%)>0.999
 Transaminase elevation2/9 (22%)1/8 (12.5%)>0.999
TTG IgA
 Mean±SD1.3±0.23 (n=6)121.21±80.29 (n=8)0.003
 Median1.23105.3
IgA
 Mean±SD144.75±41.67255.5±117.860.113
 Median152233.5
Upper endoscopy features
 Inflammation6/9 (67%)2/6 (33%)0.153
 Mucosal atrophy1/9 (11%)2/6 (33%)0.523
 Mucosal ulcers/erosions1/9 (11%)2/6 (33%)0.523
 Scalloping1/9 (11%)0/6 (0%)>0.999
 Normal duodenum0/9 (10%)1/6 (17%)>0.999
Histological features at diagnosis
 Moderate-to-severe villous blunting9/9 (100%)5/6 (83%)0.4
 Increased IELs2/9 (22%)4/6 (67%)0.135
 Increased LP cellularity9/9 (100%)6/6 (83%)>0.999
 Neutrophilic duodenitis9/9 (100%)5/6 (83%)0.4
 Surface erosion/ulceration5/9 (56%)5/6 (83%)0.58
  • *The p value was calculated by Student’s t-test and analysis of variance method for numerical covariates and Fisher’s exact for categorical covariates where appropriate. Time to symptoms onset is defined as time between the first dose of ICI and the development of symptoms. Combined therapy denotes that patients recieved ipilimumab and a programmed cell death receptor (ligand)-1 (PD-(L)1) inhibitor as standard of care or on an investigational protocol. All laboratory testings listed under ‘extraintestinal manifestations’ were performed between 2 weeks prior to establishing the diagnosis and 1 year after. Vitamin B-12 deficiency was defined as a vitamin B-12 level less than 200 ng/mL. Vitamin D deficiency was defined as a 25-OH vitamin D level less than 20 ng/mL. Iron deficiency was defined as a ferritin level less than 15 ng/mL at any hemoglobin level or a transferrin saturation less than 16%. Folate deficiency was defined as a serum folate concerntration of less than 2 ng/mL. Transaminase elevation were defined as alanine aminotransferase level higher than 33 units/L for males and 29 units/L for females. For patients with a tTG IgA level below the lower limit of the assay (less than 1.2 IU/mL), a level of 1.2 IU/mL was used for statistical calculations. Endoscopic features were all assessed on the first endoscopic evaluation of the patient at presentation. Features of inflammation included erythema, congestion, and granularity. Mucosal atrophy includes features of atrophy and loss of mucosal folds. No pathological change denotes a normal duodenum. All of the boldfaced numbers should be statistically significant and statistical significance is at p value of less than 0.05.

  • BRBPR, bright red blood per rectum; CTLA-4, cytotoxic T cell associated antigen 4; IEL, intraepithelial lymphocytes; IgA, immunoglobulin A level at diagnosis; LP, lamina propria; tTG IgA, IgA antitissue transglutaminase antibodies at diagnosis.