BACKGROUND: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy.
METHODS: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed.
CONCLUSIONS: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

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BACKGROUND: Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma.
METHODS: Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained.
RESULTS: Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein-Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively.
CONCLUSIONS: This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.

Antagonists of tumour necrosis factor α (TNFα) are a common therapeutic choice for autoimmune diseases. Although they are effective and relatively safe, an increasing number of immune-mediated adverse events have been reported. Among these, neurological adverse effectsm such as consisting of demyelinating events in the central and peripheral nervous system were described. Demyelination of the central nervous system is a rare complication after treatment with TNFα antagonists. Here, we report a case of multiple sclerosis under treatment with TNFα antagonists and discuss its etiopathogenesis. This 45-year-old female patient developed signs and symptoms suggestive of primary progressive multiple sclerosis during treatment with adalinumab for nodular cystic acne, and magnetic resonance imaging of the patient showed typical lesions of demyelinating disease.

We report the first case of a reversible rapidly progressive dementia occurring in a patient with ankylosing spondylitis, a few months after the beginning of a TNFα inhibitor treatment (TNFi). The exhaustive neurologic explorations were negative. No etiology was found to explain dementia. The dementia slowly improved after TNFi withdrawal. The chronology of this observation suggests a responsibility of the TNFi in the dementia manifestations.

Myasthenia gravis (MG) is an autoimmune disease characterised by the presence of acetylcholine receptor antibodies and by blocking the transmission of the signal in the neuromuscular junction causing muscle weakness. It can be associated with several autoimmune diseases and certain drugs, between them Etanercept an anti-tumour necrosis factor (TNF) agent. A 42-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate, was treated with adalimumab (ADA), a human monoclonal antibody against the TNF, in a dosage scheme of 40 mg every 14 days subcutaneously. The patient responded well to ADA therapy with sustained remission for 18 months when she developed blurred vision and eyelid ptosis of the left eye. The diagnosis of ocular MG was made. ADA has been discontinued and she started a treatment with pyridostigmine showing an excellent response and complete remission within a 2-month period. This is the first report making an association of ADA and ocular MG. Thus, rheumatologists dealing with patients treated with TNF inhibitors should be aware of the possible development of neurological adverse events, among them MG.

OBJECTIVE: The effects of vedolizumab [VEDO] exposure on perioperative outcomes following surgery for inflammatory bowel disease [IBD] remain controversial. The aim of our study was to compare postoperative morbidity of IBD surgery following treatment with VEDO vs other biologics or no biologics.
METHODS: An institutional review board-approved, prospectively collected database was queried to identify all patients undergoing abdominal surgery for IBD between August 2012 and May 2017. The impact of VEDO within 12 weeks preoperatively on postoperative morbidity was initially assessed with univariate and multivariable analyses on all patients. A case-matched analysis was then carried out comparing patients exposed to VEDO vs other biologic agents, based on gender, age ± 5 years, diagnosis, date of surgery ± 2 years, and surgical procedure.
RESULTS: Out of 980 patients, 141 received VEDO. The majority of patients [59%] underwent surgery involving end or diverting ostomy creation. The initial multivariate analysis conducted on all patients indicated that VEDO use was independently associated with increased overall morbidity [p <0.001], but not infectious morbidity [p = 0.30]. However, the case-matched comparison of 95 VEDO-treated patients vs 95 patients treated with adalimumab or infliximab did not indicate any difference in overall morbidity [p = 0.32], infectious complications [p = 0.15], or surgical site infections [p = 0.12].
CONCLUSIONS: In a study population having a high rate of surgery involving ostomy creation, the exposure to preoperative VEDO was not associated with an increased morbidity rate when compared with other biologics.

Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non-HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor-α inhibitors cases of this complication have increased. We report the case of a 54-year-old, HIV-negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated. After the third dose he developed PCP that required admission to the intensive care unit, with a positive response to i.v. administration of trimethoprim/sulfamethoxazole. During follow up a mutation in the IL36RN gene compatible with an IL-36RN deficiency was found and anakinra was started, with rapid improvement of his psoriasis. PCP is a severe complication in patients receiving immunosuppressive therapy and is probably underreported by dermatologists. There are no clinical guidelines for PCP prophylaxis in dermatological patients who will receive immunosuppressive or biological treatments. We believe that it is necessary to report the cases of PCP to assess the real impact of this complication and develop appropriate prophylaxis guidelines.