TABLE 2.
Cases reported with the use of anti-CD20 and IBD in patients with non-MS conditions.
| References | Age (sex) | Disease | Anti-CD20 | Time to symptoms | Clinic | Complementary tests | Histopathology | Treatment | Follow-up |
|---|---|---|---|---|---|---|---|---|---|
| Klug et al. (2022) | 27 (F) | LP, UC, SC | RTX | 2 months | Fever, abdominal pain, bloody diarrhoea | CT-PET: pancolonic hypermetabolism | Not available | Low dose corticoids | Clinical improvement |
| CT: lead-pipe image | |||||||||
| el Fassi et al. (2008) | 45 (F) | GD | RTX | 7 days | Bloody diarrhoea, fever and joint pain | End.: UC | Mucosal inflammation, irregular crypts and cryptic abscesses with no granulomas. Absence of CD20+ cells. Persisting plasma cells and T cells | Prednisolone enemas during 14 days followed by 5-ASA for maintenance | Clinical improvement |
| HLAB27-pANCA+ | Restoration of CD20+ cells levels on biopsy after 3 months of treatment | ||||||||
| Tsuzuki et al. (2021) | 65 (M) | Gastric maltoma | RTX | 4 months | Watery and bloody diarrhoea | CT: longitudinal hypertropia from terminal ileum to rectum | Wide inflammation with diffuse circumferential erosions, epithelial atrophy, cryptitis and cryptical abscess without granulomas. Lymphocytic infiltration with atypical lymphocytes and intraepithelial lymphocytes (similar to MC). No CD20+ cells. Presence of CD3+T, CD79a+B and CD68+ cells | Oral prednisolone during 2 weeks followed by tappering dose | Clinical improvement with complete symptom resolution after 3 months of treatment. Endoscopic improvement after 5 months of treatment |
| End.: hyperaemia end erosions in gastric antrum; patchy ulcers with diffuse inflammation in terminal ileum and colon | |||||||||
| Cavalcanti et al. (2020) | 45 (M) | Gastric ADC and NHL | RTX | Not available | Watery and bloody diarrhoea and abdominal pain | PET: hypermetabolism in terminal ileum and mesenteric lymph nodes | Nonspecific active ileitis | RTX discontinuation | Clinical worsening after additional RTX cycles. Good response to RTX withdrawal, budesonide and 5-ASA. |
| End.: erythema, aphthous erosions and inflammation in terminal ileum | After additional RTX cycles: chronic active inflammation, cryptical abscess, granulation tissue in lamina propria. Total depletion of CD20+ cells in ileal mucosa with increase of CD3+ T cellularity intraepithelial and in lamina propria with moderate excess of enlarged macrophages in lamina propria | Budesonide and 5-ASA followed by 5-ASA for maintenance | At week 10, asymptomatic with good endoscopic control. After 30 months with 5-ASA still in remission | ||||||
| Shankar et al. (2019) | 58 (F) | Tonsillar FL | RTX | 3 years | Bloody diarrhoea, abdominal pain, oral ulcers and nodous erythema | PET: hypermetabolism in terminal ileum and mesenteric lymph nodes | Nonspecific severely active ileitis with non-caseating granulomas | Oral prednisone and ustekinumab (induction and manteinance) | 4 weeks: pain and nodous erythema resolution with CRP and ESR normalization |
| End.: inflammation with extensive ulceration in terminal ileum | 6 months: End.: no inflammation signs, nor fistulas nor stenosis. PET: without activity in terminal ileum | ||||||||
| After additional RTX cycles | |||||||||
| PET: new activity in sigmoid colon | |||||||||
| Entero-MRI: ileo-colic fistula | |||||||||
| Barreiro Alonso et al. (2019) | 55 (M) | MCL | RTX | 2 years | Watery diarrhoea | End.: erythematous colon mucosa from rectum to cecum with some oedema and exudate. Erythematous terminal ileum with isolated ulcers | Nonspecific active chronic colitis and nonspecific chronic ileitis with granulation tissue | Loperamide | Clinical improvement with 5-ASA |
| 5-ASA after cessation of RTX | |||||||||
| Morita et al. (2019) | 15 (M) | RNS | RTX | 2 years | Abdominal pain, watery diarrhoea, weight loss and oral aphtas | CT: mural circumferential thickening from ileocecal union to ascending colon | Chronic colitis with severe active inflammation without granulomas nor inclusion bodies nor caseous necrosis | Mouth wash with 5-ASA and fasting therapy with parenteral nutrition | Clinical improvement after 5-ASA and fasting therapy |
| End.: multiple punched-out ulcers and cobblestone pattern in ascending colon with patchy erosions from transverse colon to rectum. In endoscopic video-capsule, multiple erosions in small intestine | Infliximab for maintenance without cessation of RTX | No recurrence of nephrotic syndrome or Crohn’s disease after maintenance with infliximab and RTX. | |||||||
| Uzzan et al. (2018) | 25 (F) | DLBCL | RTX | 6 months | Epigastric pain | End.: normal colonic mucosa | Absence of CD20+ cells in plasma and colon lamina propria with normal T cells and plasma cells. Significant increase in CD19+ cells population (almost exclusively CD38hiCD27+ -gut resident plasma cells-, mostly IgA+). Lower CD19-/CD19+ ratio than controls | - | - |
| Varma et al. (2017) | 80 (F) | SCL | RTX | 3 months | Diarrhoea and fever | PET: ileal hypermetabolism | Patchy active mucosa inflammation with ulceration and multiple small granulomas, some of them with multinucleated giant cells | Budesonide | |
| End.: abnormal proliferative tissue and ulcers in ileocolic union, isolated ulcer in hepatic angle and left colon | Surgical removal of ileocolic union mass, observing small intestine involvement and fistulas | ||||||||
| CT: inflammatory mass in right colon | |||||||||
| 74 (F) | NHL | RTX | 2 years | Diarrhoea, abdominal pain, fever, weight loss and right iliac fossa pain | CT: terminal ileal mural thickening | Active ileitis with ulceration. Active focal mucosal inflammation with ulcer and granuloma in right colon | Budesonide | Recurrence of fever and abdominal pain after 3 weeks. Initiation of hydrocortisone iv and tappering dose of oral prednisone and methotrexate | |
| End.: ileal inflammation, lineal ulceration. Normal colon mucosa | |||||||||
| Fraser et al. (2016) | 24 (F) | GPA | RTX | 2 years | Perineal ulceration | End.: normal colon mucosa | Perineal skin: mixted inflammatory infiltrate | Infliximab and azathioprine | Fistula resolution |
| MRI: acute inflammation | Colon: mild inflammatory changes with focal cryptitis with eosinophilic preponderance (no typical for IBD) and cryptical abscess | ||||||||
| After new RTX cycle | After new RTX cycle: perineal skin: granulomas (CD) | ||||||||
| MRI: wide fistulizing disease with recto-vaginal fistula | |||||||||
| Lipka et al. (2016) | 62 (F) | MZL | RTX | Not available | Abdominal pain and diarrhoea | CT: diffuse colonic mural thickening with abdominal distension and areas of pneumatosis | Severe inflammation | Subtotal colectomy | Five years later, having received four RTX cycles due to lymphoma recurrence, proctectomy was needed because of clinical recurrence |
| Bhalme et al. (2013) | 38 (F) | RA | RTX | 11 weeks | Bloody diarrhoea | End.: moderate-severe colitis | Goblet cells depletion, active chronic inflammation and cryptical abscess. No CD20+ cells, low levels of CD19+ cells. Plasma cells and CD3+ CD138- T cells present | Corticoids and 5-ASA. | Lymphocytic restoration with biopsy and endoscopic normalization |
| RTX discontinuation | |||||||||
| Sekkach et al. (2011) | 34 (M) | B-SLE | RTX | 3 weeks | Abdominal pain, nausea, watery diarrhoea | CT: intestinal mural thickening | Not conclusive for IBD. | RTX cessation | Complete resolution |
| End.: erythematous-ulcerative pancolitis | CD20+ cell depletion in appendix biopsy | ||||||||
| el Fassi et al. (2011) | Age not available (F) | GD | RTX | 18 months | Diarrhoea | End.: low grade colonic inflammation | Follow-up with normal barium studies | ||
| Age not available (F) | GD | RTX | After 2nd infusion | Bloody diarrhoea | End.: UC in distal colon | - | 5-ASA | Endoscopic normalization. Colonic B cell restoration after 170 days | |
| ANCA low titers | |||||||||
| Vallet et al. (2011) | 66 (F) | RA | RTX | 2 years | Mucous diarrhoea | CT: mesocolon inflammation | - | Ganciclovir for 7 days | Diarrhoea resolution after the first week of treatment. |
| End.: superficial ulcerations | Valaciclovir for 14 days plus human Ig iv. infusion | ||||||||
| CMV + | |||||||||
| Plasma: Absence of B cells, normal T cells, IgG 2.77 g/L | |||||||||
| Ardelean et al. (2010) | 4 (M) | RNS | RTX | 6 weeks | Abdominal pain, weight loss, bloody diarrhoea, oral ulcers, intermittent fever | Abdominal echography: severe pancolitis with mural thickening | Focal areas of cryptitis and inflammatory infiltrate in lamina propria with lymphocytes, plasma cells and some eosinophils, without granulomas or giant cells. Absence of CD19+ and CD20+ cells. Activation of mature CD3+ T cells, cytotoxic CD8+ T cells and Treg FOXP3+ cells | Prednisone with posterior tappering dose | Recurrence of diarrhoea after cessation of prednisone. Restoration of prednisone during 2 months and addition of azathioprine. After 7 months, endoscopic resolution |
| End.: grade IV severe inflammation with deep ulcerations from descending colon to rectum. Moderate grade II-III inflammation in ascending colon | After 11 months, CD19+ and CD20+ cells levels were restored | ||||||||
| Goetz et al. (2007) | 58 (M) | UC | RTX | Days | Bloody diarrhoea, weight loss and fever | End.: severe continuous colitis from anus to sigmoid colon, with spontaneous bleeding, ulcers, oedematous granular mucosa and loss of haustration. Low CD20+ cell levels in plasma. | Dense monocytic inflammatory infiltrate in mucosa with CD3+ T cells and complete depletion of CD20+ cells. In lamina propria mononuclear cells culture: absence of IL-10 | RTX cessation 5-ASA, corticoids and ciprofloxacin | Partial recovery |
| Blombery et al. (2011) | 67 (M) | FL | RTX | 2 months | Fever, cough, dyspnoea, watery and bloody diarrhoea | CT: lung consolidation, pancolitis and ileitis with diffuse colonic mural thickening and pericolic stranding adjacent to cecum and ascending colon End.: severe confluent inflammation from anorectal union to proximal border at 30 cm in sigmoidoscopy | Complete loss of tubules and almost complete loss of superficial epithelium without pseudomembranes. Moderate mononuclear infiltrate in lamina propria with some eosinophils. No submucosal involvement. Absence of CD20+ cells with CD3+ cells normal or elevated and CD68+ cells (macrophages) elevated | Hydrocortisone iv | Clinical worsening requiring subtotal colectomy 2 weeks after the onset of the symptoms. Finally, the patient died 4 weeks after due to pneumonia |
5-ASA: 5-aminosalicylic acid or mesalazine; ADC: adenocarcinoma; B-SLE: bullous systemic lupus erythematosus; CD: Crohn’s disease; CRP: C reactive protein; CT: computerized tomography; DLBCL: Diffuse large B-cell lymphoma; End.: endoscopy; ESR: erythrocyte sedimentation rate; FL: follicular lymphoma; GD: Graves’ disease; GPA: granulomatosis with polyangiitis; LP: lymphoproliferative disease; MC: microscopic colitis; MCL: mantle cell lymphoma; MZL: Marginal zone B-cell lymphomas; NHL: non-Hodgkin lymphoma; PET: positron emission tomography; RA: rheumatoid arthritis; RTX: rituximab; SC: sclerosing cholangitis; SCL: small cell lymphoma; RNS: refractory nephrotic syndrome; UC: ulcerative colitis.