Clinical Case Summary

A 59-year-old male with ulcerative colitis presented with steroid-dependent disease with adverse reactions to sulfasalazine and azathioprine. Vedolizumab was started in 2018 but switched to Adalimumab from October 2020 for symptomatic flare with active endoscopic inflammation. In June 2022, despite supratherapeutic Adalimumab levels without anti-drug antibodies, elevated biomarkers with persistent endoscopic activity prompted restarting Vedolizumab alongside Adalimumab. Financial constraints and ischemic heart disease precluded the use of Ustekinumab and Tofacitinib respectively.
In January 2023, his previously normal platelet count dropped to 56x10⁹/L. Despite stopping Adalimumab, this fell further to a nadir of 16x10⁹/L over one month. Other cell lines were unaffected. He remained in clinical remission and had no bleeding manifestations.
Anti-nuclear antibodies and anti-double-stranded DNA antibodies returned positive. Complement levels, C-reactive protein, urine studies and renal function, however, remained normal. Rheumatology deemed drug-induced lupus unlikely, given the absence of clinical features and noting the not uncommon development of autoantibodies with anti-tumour necrosis factor (TNF) use. Bone marrow examination, arranged after Haematology consult, showed normocellular marrow without evidence of lymphoproliferative or myeloproliferative disorders. Our patient was eventually diagnosed with immune thrombocytopenia and started on Prednisolone at a dose of 1mg/kg/day. He responded well to steroids with normalisation of his platelet count within one week and remains well on follow up with tapering steroids and Vedolizumab.
Immune thrombocytopenia is a rare but significant complication of anti-TNF use. Posited mechanisms include anti-TNF interaction with platelet membrane glycoprotein receptors with antibody formation and excess Th2 lymphocyte antibody production. Anti-TNF cessation and systemic corticosteroids are the cornerstones of treatment.

References

Table 1. Platelet count trend in relation to Adalimumab cessation and corticosteroid initiation.

Clinical Case Summary

The introduction and increasingly wide use of immune checkpoint inhibitors in the treatment of malignant diseases has been revolutionary in the last decade. However, as these inhibitors alter immunity through T-cell modulation, immune-related adverse events(irAEs) driven by the very same immunologic mechanisms responsible for the therapeutic effects might occur.
Herein, we present a case of a 42 year-old woman with locally advanced melanoma who developed a number of concomitant irAEs: pancreatitis, colitis, hepatitis, thyroiditis but the most rare and the most severe of them was immune checkpoint inhibitor- related gastritis. This patient presented with diarrhea, nausea, vomiting, weight loss, and reduced oral intake for two weeks. She had previously been treated with 16 doses of nivolumab, then switched to combination of nivolumab/ipilimumab due to progression of the melanoma.
Diagnosis was confirmed with oesophagogastroduodenoscopy (OGDS), computed tomography(CT) scan and biopsy. The patient was treated with proton pump inhibitor combined with methylprednisolon for 2 weeks without improvement, after which Mycofenolate mofetil was added again without improvement of symptoms. Considering the severity of the irAEs, immunotherapy was discontinued definitively.
We started salvage therapy with Infliximab in a dose of 5mg/kg - two applications at week 0 and week 2 with minor improvement confirmed with a second OGDS. Local radiotherapy was initiated. Despite the multidisciplinary approach the patient's condition continued to worsen and head CT scan noted brain metastasis. The patient died shortly afterwards.

References

endoscopic images, computed tomography images, histological images

Disclosure

no conflict of interest

Clinical Case Summary

Introduction: Since the covid-19 pandemic, there has been a significant resurgence of tuberculosis in endemic countries. As a result, extremely rare localizations of tuberculosis have appeared. Stomach involvement is rarely seen in gastrointestinal tuberculosis. The clinical presentation can be either alarming symptoms (anorexia, weight loss...), or a complication (digestive hemorrhage, perforation). In front of the weight loss and the alteration of the general state, the diagnosis is often directed towards a neoplastic pathology, which represents a diagnostic challenge.

Clinical case: We received in our institution a 77-year-old woman, referred from the emergency room for hematemesis with epigastric pain. She had experienced important weight loss during the last month. The clinical examination was unremarkable, and blood tests was normal, despite an hemoglobin of 8,7 g/dl. An upper endoscopy was performed, which showed the existence of 3 ulcerations localized on the greater curvature of the stomach, the largest measuring 4 centimeters. Biopsies of the ulceration borders were performed. Histology revealed the presence of an epithelio-giganto-cellular granuloma with caseous necrosis.
The final diagnosis was gastric tuberculosis. We started an antituberculosis therapy, with a proton pump inhibitor, with significant improvement within one month.

Conclusion: In conclusion, gastric tuberculosis, even if it is a rare entity, should be considered when gastric signs are associated with signs of tuberculosis impregnation, especially in endemic countries. The endoscopic signs are not specific, only histology can establish a reassuring diagnosis. Our patient was successfully treated by Antitubercular drug despite the severity of his bleeding.

References

Endoscopic images showing tow small gastric ulcers and a large gastric ulcer of the greater curve of the stomach
Histological image showing epithelio-giganto-cellular granuloma with caseous necrosis

Clinical Case Summary

Introduction: Tofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data.
Case description: We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia.
Conclusion: Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about type IVb hypersensitivity reaction as an AE of tofacitinib not reported so far. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC.

Introduction

The incidental finding of terminal ileal inflammation during routine colonoscopy is not uncommon and is of unclear significance. It has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. There is limited data on long term follow-up and outcomes of such findings.(1)

Aims & Methods

This is a monocentric retrospective observational study spanning from 2018 to 2023, comparing two periods: the first period (P1) before the impact of the Covid-19 pandemic in 2020, and the second period (P2) starting 2020 reflecting the impact the pandemic left on colonoscopies. For each patient, variables were collected from medical records.

Results

Our initial database included 11200 colonoscopies, from which we randomly selected 2394 patients proportionally to the annual activity (mean of 1686/year before 2020 and 1189/year after 2020). Among indications of colonoscopy were screening and follow-up, change in bowel habits, anemia and bleeding. We excluded 287 patients (known history of inflammatory bowel disease and no ileum intubation). Then the sample was divided into P1 (681 patients) and P2 (1483 patients). Characteristics and findings are shown in Table 1. We noted better bowel preparation (77.1 vs 91.7%) and a higher ileum intubation in P2 (79.7 in P1 vs 93.8% in P2).
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N=2164			P1 (N1=681)	P2 (N2= 1483)	p
Age (years)			57.5	56.9	NS
Overall endoscopic findings n(%)	Endoscopic aspect of ileitis		0 (0)	71 (5.8)	<0.001
	Abnormal ileal findings on histology		23 (3.4)	169 (11.4)	<0.001
	Diagnosis of Crohn's disease		0 (0)	19 (0.9)	<0.001
Overall histological findings n(%)	Active ileitis		19 (2.8)	147 (9.9)	<0.001
	Focal ileitis		10 (1.5)	89 (6)	<0.001
	Ulcerative ileitis		11 (1.6)	48 (3.2)	0.031
	Erosive ileitis		3 (0.4)	31 (2.1)	0.004
	Architectural distortion		1 (0.1)	16 (1.1)	0.023

Overall ileoscopy findings showed an increased aspect of ileitis on endoscopy (0% in P1 and 5.8% in P2, with p<0.001), correlating with a significant increase in the incidence of histological findings on ileal biopsies (3.4% in P1 vs 11.4% in P2; p<0.001). These histological findings included active, focal and ulcerative ileitis, with more architectural distortion. However, these results corresponded to a less severe ileitis (0.3 vs 2.3%; p=0.001). Nineteen of these patients with positive results of ileitis were diagnosed with Crohn’s disease.

Conclusion

This study showed an increase in endoscopic and histologic ileitis on colonoscopy following the Covid-19 era. This could be the result of the direct virologic effect that the virus has on intestinal inflammation, its indirect effect on immunity triggering the onset of enteritis, or the consequence of the mass vaccination campaign held to protect from the virus. Furthermore, histology showed granulomatous inflammation similar to Crohn’s disease, which may lead to misdiagnosis and probably overtreatment.

References

1. Agrawal M, Miranda MB, Walsh S, Narula N, Colombel JF, Ungaro RC. Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis. J Crohns Colitis. 2021 Feb 14;15(9):1455–63.