Noninfectious gut inflammation is a common manifestation of inborn errors of immunity (IEI) and can affect various segments of the gastrointestinal tract. Vedolizumab, which selectively blocks leukocyte trafficking to the gut, is approved for treatment of inflammatory bowel disease; however, there is lack of data regarding safety and efficacy in IEI. We aim to describe the experience of patients with gut inflammation related to IEI treated with vedolizumab.
4 patients >18 years old with humoral or combined immunodeficiency and gut inflammation treated with vedolizumab (weeks 0, 2, and 6, and then every 8 weeks) at a tertiary center. Clinical improvement was defined as a reduction in diarrhea reported by patients with weight gain and/or improvement of malabsorption.
Case 1: 37-year-old man, combined immunodeficiency with dysregulation due to TRAF3 haploinsufficiency. He had a long-standing enteropathy with duodenal, ileal, and colonic involvement and was corticosteroids dependent. He started vedolizumab, achieving good symptomatic control. After one year of treatment, mild endoscopic activity was observed, so he added a low dose of corticosteroids, resulting in clinical improvement.
23-year-old man, combined immunodeficiency with dysregulation, WES negative. He presented chronic diarrhea, weight loss, and malabsorption requiring hospitalizations in context of complete villous atrophy with poor response to corticosteroids. A clear clinical response was observed after induction with 3 doses of vedolizumab.
49-year-old woman, CVID with autoimmune hepatitis and chronic severe colitis refractory to topical and oral corticosteroids and azathioprine. She received four doses of vedolizumab without clinical improvement, eventually developing extensive pancolitis due to CMV. She is being considered for a subsequent treatment line with ustekinumab.
51-year-old woman, persistent agammaglobulinemia after rituximab treatment for immune thrombocytopenia and multiple other autoimmune manifestations, WES pending. Chronic diarrhea with complete villous atrophy refractory to corticosteroids. After 5 doses of vedolizumab, she exhibited clinical and endoscopic improvement and remained free of atrophy for two years. After this period, partial villous atrophy recurred.
We observed a more favorable and sustained effect of vedolizumab on duodenal atrophy compared with colitis, emerging as a safe option for patients with immunodeficiency and enteropathy.
Clinical and immunological features.
| Case 1 | Case 2 | Case 3 | Case 4 | |
|---|---|---|---|---|
| Age of first symptoms (years) | 15 | 1 | 38 | 26 |
| Age of first gastrointestinal symptoms (years) | 17 | 19 | 38 | 29 |
| Extraintestinal clinical features | Recurrent RTI, warts, penile intraepithelial neoplasia, polyarthritis | Recurrent RTI, bronchiectasis, HSM, portal hypertension, Hodgkin lymphoma, short stature | Autoimmune hepatitis, esophageal candidiasis, recurrent RTI | ITP, splenectomy, thyroiditis, vitiligo, alopecia areata, CMV pneumonia, severe COVID-19 |
| Immunoglobulin levels | ||||
| IgG (800-1700 mg/dL) | 673 | <200 | 370 | <200 |
| IgA (70-400 mg/dL) | 57 | <4 | 36 | <4 |
| IgM (50-300 mg/dL) | 32 | 8 | 19 | <10 |
| IgE (0.1-100 UI/mL) | 2 | <0.1 | <0.1 | |
| Antipneumococcal response | Absent | Poor response | Poor response | Absent |
| Lymphocyte subsets (cel/uL) | ||||
| CD19+ (110-570 cel/uL) | 515 (22%) | 8 (0.9%) | 3 (0.3%) | 1 (1%) |
| CD4+ (530-1300 cel/uL) | 196 (28%) | 123 (14%) | 281 (36%) | 358 (42%) |
| CD8+ (330-920 cel/uL) | 413 (59%) | 687 (86%) | 337 (43%) | 275 (32%) |
| CD56+ (70-597 cel/uL) | 70 (3%) | 75 (8.4%) | 181 (21%) | 221 (26%) |
HSM: hepatosplenomegaly. RTI: respiratory tract infection.
Endoscopic and biopsy findings before and after treatment with vedolizumab.
| Findings before treatment | Findings after treatment | |
|---|---|---|
| Case 1 | Duodenum: complete villous atrophy (Marsh IIIc). Active duodenitis | Duodenum: absence of villous atrophy. Active duodenitis |
| Ileum: follicular hyperplasia, chronic ileitis | Ileum: follicular hyperplasia | |
| Colon: chronic active colitis | Colon: absence of inflammatory activity | |
| Rectum: focal active colitis | ||
| Calprotectin: 2065 ug/g | Calprotectin: 838 ug/g | |
| Case 2 | Duodenum: complete villous atrophy (Marsh IIIc). Intraepithelial lymphocytosis >25%, absence of plasmocytes | Pending results |
| Case 3 | Duodenum: absence of villous atrophy and lymphocytosis | Colon: severe active colitis, with viral inclusions |
| Ileum: follicular hyperplasia, active ileitis | ||
| Colon: severe active chronic colitis, increased apoptosis and absence of plasmocytes | ||
| Calprotectin: 371 ug/g | ||
| Case 4 | Duodenum: complete villous atrophy (Marsh IIIc). Intraepithelial lymphocytosis >30% | Duodenum: absence of villous atrophy and lymphocytosis |
| Ileum: follicular hyperplasia | ||
| Colon: absence of inflammatory activity | Colon: absence of inflammatory activity | |
| Calprotectin*: 332 ug/g | Calprotectin: 203 ug/g |
Normal range: 5-45 ug/g
