Sex: M
Vaccine: UNK
Symptoms: Polymerase chain reaction
Clinical narrative: ulcerative colitis; Inflammatory bowel disease; ulcerative colitis flare; Increased stool frequencyand urgency; This case was reported in a literature article and described the occurrence of ulcerative colitis in a 63-year-old male patient who received Herpes zoster (Shingrix) for prophylaxis.   Previously administered products included mesalamine (revived 29 weeks prior to the recombinant herpes zoster vaccine (RZV)), budesonide, infliximab, prednisone (last taken 29 weeks prior to patient's first RZV dose)) and vedolizumab (Twenty-two weeks prior to first RZV dose switched from infliximab to vedolizumab). Concurrent medical conditions included ulcerative colitis (left-sided , diagnosed 2 year prior the time of reporting). Concomitant products included Herpes zoster (Shingrix), methotrexate and vedolizumab.   On an unknown date, the patient received the 2nd dose of Shingrix. On an unknown date, 3 days after receiving Shingrix and an unknown time after starting Interleukin 2, the patient experienced ulcerative colitis (serious criteria GSK medically significant), bloody diarrhea (serious criteria GSK medically significant), condition aggravated and increased stool frequency. The subject was treated with interleukin-2 (Interleukin 2), prednisone and tofacitinib. On an unknown date, the outcome of the ulcerative colitis, bloody diarrhea, condition aggravated and increased stool frequency were unknown.   The reporter considered the ulcerative colitis, bloody diarrhea, condition aggravated and increased stool frequency to be possibly related to Shingrix.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of ulcerative colitis flare in a male patient aged 63-year-old who was vaccinated with Shingrix (recombinant herpes zoster vaccine RZV)) (GlaxoSmithKline) for prophylaxis.  The patient was a part of prospective observational study of patients with IBD who received RZV between February 2018 and July 2019 at a tertiary IBD referral center and aimed to assess in a prospective manner the rate of IBD flare as well as adverse reactions after administration of RZV in a cohort of patients with IBD. The patient had a history of left-sided UC, no previous history of herpes zoster (HZ), and no previous vaccination with zoster live-attenuated vaccine (ZVL). The patient was diagnosed with ulcerative colitis (UC) 2 years prior and had failed mesalamine, budesonide multi matrix (MMX), infliximab, and prednisone (last taken 29 weeks prior to patient's first RZV dose). The patient's IBD type and location, and most recent IBD activity score prior to vaccination was abstracted from electronic medical records. Twenty-two weeks prior to first RZV dose, the patient was switched from infliximab to vedolizumab and remained on oral methotrexate due to ongoing symptoms, an elevated fecal calprotectin of 345.1 microg/g, and a colonoscopy showing moderate to severe left-sided UC. Pathology revealed chronic colitis with mild to moderate activity. The patient's UC improved, and two days prior to the first RZV dose, the patient was noted to be in clinical as well as endoscopic remission (Mayo 1 on flexible sigmoidoscopy) on vedolizumab for 33 weeks before experiencing the flare. Pathology showed mild architectural changes without active inflammation. No information on patient's family history was provided. On an unspecified date between February 2018 and July 2019, the patient received 1 dose of Shingrix (administration route and site unspecified, batch number not provided). [In this study, In October 2017, a two-dose recombinant HZ vaccine (RZV; Shingrix) containing recombinant VZV glycoprotein E and AS01B, a liposome-based adjuvant system, was approved by the Food and Drug Administration for prevention of HZ in adults aged more than equal to 50 years. The Advisory Committee on Immunization Practices recommends RZV only in adults aged more than equal to 50 years that were immunocompetent or on low-dose immunosuppressant therapy equivalent to less than 20 mg/day of prednisone]. The age of vaccination was not provided but it could be between 62 and 63 years.  On an unspecified date, the patient was followed-up during office visit or phone call, scheduled approximately 14 days after administration of 1st dose of Shingrix in order to capture vaccine-related symptoms within a reasonable time frame and was reported to have tolerated without disease flare. On an unspecified date between February 2018 and July 2019, 10 weeks after the 1st dose, the patient received 2nd dose of Shingrix (administration route and site unspecified, batch number not provided). The age of vaccination was not provided but it could be between 62 and 63 years. On an unspecified date between February 2018 and July 2019, 3 days after 2nd dose of Shingirx, the patient developed recurrent colitis symptoms of bloody diarrhea with increased stool frequency and urgency. Workup of the patient's symptoms included normal complete blood count (CBC), normal comprehensive metabolic panel (CMP) except for mildly elevated alkaline phosphatase at 110 u/L, mildly elevated C-reactive protein (CRP) at 6.2 mg/L, elevated fecal calprotectin at 887.2 microg/g, and negative Clostridium difficile (C Diff) toxin polymerase chain reaction (PCR). The patient's IBD activity scores (Harvey Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI)) increased and local and systemic reactions were solicited during follow-up office visit or phone call, scheduled approximately 14 days after administration of 2nd dose of RZV in order to capture vaccine-related symptoms within a reasonable time frame. [In this study, the primary outcome was rate of IBD flare following vaccination. IBD flare was defined as an increase in IBD activity score (HBI or SCCAI) resulting in either an increase in dose of any maintenance IBD medication or initiation of a new corticosteroid or biologic medication. The secondary outcomes were rates of local and systemic adverse reactions after vaccination. Local and systemic adverse reactions were reported in 74.6% and 56.7% of patients, respectively]. The patient was diagnosed with ulcerative colitis flare with no HZ infection. Prednisone was started, and due to a low trough vedolizumab drug level at 7.6 microg/ml without antidrug antibodies, vedolizumab frequency was increased to every 4 weeks. No improvement was seen after 8 additional weeks, prompting a computed tomography (CT) enterography and colonoscopy, which confirmed active left-sided UC with moderate to severe chronic active colitis on biopsy. The patient's symptoms were refractory to various additional medical therapies, including a trial of tofacitinib, a prednisone taper, and 3 months of daily subcutaneous interleukin (IL)-2 injections as part of an open-label study. Due to continued symptoms and refractory to various escalated medical therapies, the patient underwent a total colectomy with ileostomy 10 months after the second dose of RZV.  Outcome of the event was not reported. The authors commented "One hypothesis that cannot be excluded was that his disease flare may have been induced by a secondary immune response from the second RZV dose. During a secondary immune response, repeat exposure to a previously encountered antigen produces a stronger and faster inflammatory response through activation of B and T lymphocytes and antibodies. Initial sensitization may have occurred from a component of the first RZV dose, and repeat exposure during the second RZV dose may have produced an immune response, resulting in an UC flare. The alternative explanation was that the patient flared in the setting of a low vedolizumab level. Our study suggests that rates of IBD flare were not increased by RZV administration. In this cohort, 74.6% of patients had injection-site reactions, and 56.7% of patients had systemic reactions after RZV administration. We postulate that the risk of IBD flare after HepB-CpG was likely low as well, because relative improvements in vaccine efficacy suggest that the CpG-1018 adjuvant in HepB-CpG is less potent than the AS01B adjuvant in RZV. With the completion of post-licensure surveillance studies, further information on the safety of the RZV and HepB-CpG vaccines will become available.".  The authors concluded "we observed a low rate of IBD flare after RZV administration (1.5%) in a cohort of patients with IBD in which two-thirds were immunosuppressed. Rates of local and systemic adverse reactions from RZV in this cohort were also similar to those seen in the general population. These findings may provide reassurance to providers and patients that RZV is safe in a real-world setting for patients with IBD. However, further comparative studies with larger number of patients and longer follow-up are needed to confirm that IBD and other immune-mediated diseases are not worsened after RZV administration."      Lab Comments: Lab test were performed between February 2018 and July 2019. The patient had normal comprehensive metabolic panel (CMP) except for mildly elevated alkaline phosphatase , mildly elevated C-reactive protein (CRP)  and elevated fecal calprotectin No improvement was seen after 8 additional weeks, prompting a computed tomography (CT) enterography and colonoscopy, which confirmed active left-sided UC with moderate to severe chronic active colitis on biopsy. The patient's IBD activity scores (Harvey Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI)) increased.