Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

Fever of unknown origin (FUO) poses a diagnostic challenge, and 18-fluorodexoyglucose positron emission tomography with computed tomography (18FDG-PET/CT) may identify the source. We aimed to evaluate the diagnostic yield of 18FDG-PET/CT in the work-up of FUO. The records of patients admitted to Sheba Medical Center between January 2013 and January 2018 who underwent 18FDG-PET/CT for the evaluation of FUO were reviewed. Following examination of available medical test results, 18FDG-PET/CT findings were assessed to determine whether lesions identified proved diagnostic. Of 225 patients who underwent 18FDG-PET/CT for FUO work-up, 128 (57%) met inclusion criteria. Eighty (62.5%) were males; mean age was 59 ± 20.3 (range: 18–93). A final diagnosis was made in 95 (74%) patients. Of the 128 18FDG-PET/CT tests conducted for the workup of FUO, 61 (48%) were true positive, 26 (20%) false positive, 26 (20%) true negative, and 15 (12%) false negative. In a multivariate analysis, weight loss and anemia were independently associated with having a contributary results of 18FDG-PET/CT. The test yielded a sensitivity of 70%, specificity of 37%, positive predictive value of 70%, and negative predictive value of 37%. 18FDG-PET/CT is a valuable tool in the diagnostic workup of FUO. It proved effective in diagnosing almost half the patients, especially in those with anemia and weight loss.

Background: Idiopathic thrombocytopaenic purpura [ITP] is an acquired haematological disorder with an incidence of 1–6 per 100 00/year. ITP and inflammatory bowel disease [IBD] comorbidity has been reported in the literature, but insights regarding the course, outcome and optimal management are limited by its rarity. The current study aimed to evaluate the clinical presentation and outcome of ITP in patients with IBD. Methods: This multicentre retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports [CONFER] project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardized collection form. Results: This report includes 32 patients with concurrent ITP and IBD: ten were females, and the median age was 32.0 years (interquartile range [IQR] 20.5–39.5). Fourteen patients had a diagnosis of Crohn’s disease [CD] and the other 18 ulcerative colitis [UC]. The diagnosis of IBD preceded the ITP in 26 patients (median time between diagnoses was 7.0 years [IQR, 1.5–9.5]). Among those patients, 17 were in clinical remission at ITP diagnosis. Thirteen patients were treated with mesalamine, four with oral corticosteroids, one with rectal corticosteroids, two with azathioprine and five with anti-tumour necrosis factor agents. The median platelet count was 35 000/microliter [IQR, 10 000–70 000]. Eight patients had rectal bleeding, 13 had skin purpura, three had epistaxis, six had mucosal petechiae and 13 were asymptomatic. Regarding ITP treatment, 19 were treated with corticosteroids, one with anti-RhD immunoglobulin, 12 with intravenous immunoglobulins [IVIGs], four with thrombopoietin, three with rituximab and six patients eventually required splenectomy. Ten patients needed no treatment directed to the ITP. Three patients required colectomy during long-term follow-up, due to IBD or cancer but not to massive bleeding as a complication of ITP. One of eight patients who presented with rectal bleeding required splenectomy, and none required urgent colectomy. Two patients died during the follow-up, one of them due to bleeding complications located in the upper gastrointestinal tract. Median follow-up time was 6.5 years [IQR, 3–10]. With long-term follow-up, all patients had platelet counts above 50 000/microliter, and 24 were in IBD clinical remission. Conclusion: Most ITP cases in this series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients followed an expected course, including response to medical therapy and low rates of splenectomy.

To the Editors: Recent data indicate that 50% of inflammatory bowel disease (IBD) patients have used and 75% plan to use complementary medicine approaches for their IBD.¹ Moreover, some thought leaders have recognized the need to carefully weigh possible candidates for clinical adoption,² but data on IBD experts’ attitudes toward complementary medicine are still scant. We recently conducted a survey among Israeli IBD experts, exploring the current shift of attitudes toward such therapies. A questionnaire was compiled and sent by email to a representative sample of leading expert members of the National Israeli IBD Society. Overall, 40 IBD experts were approached and 25 (62.5%) responded. Respondents were all Board certified and experienced gastroenterologists. On a 7-point Likert-type standard scale (1 = not at all, 7 = very much), 76% of respondents thought that a dialogue between integrative and conventional medicine practitioners is very important (a score of 6 or 7) and 72% thought that IBD patients are very interested to learn about integrative medicine treatment options. A total of 50% of respondents reported that they frequently and 37.5% reported that they occasionally refer their patients to some form of integrative medicine. Among several popular complementary medicine compounds or regimens ( Figure 1), a combination of curcumin and Qing Dai (indigo naturalis) (CurQD) was perceived as the most evidence-based and beneficial IBD treatment.^3-6 This survey among leading national experts in IBD suggests that physicians are increasingly cognizant of patients’ interest in exploring integrative medicine therapy options. These findings also reinforce the message by Sudhakar et al² and the conclusions of a European Crohn’s and Colitis Organization⁷ topical review in calling for more cross-talk and holistic integration between well-evidenced complementary therapies and mainstay medical interventions for our IBD patients.

Patients with Crohn’s disease (CD) are frequently subject to symptoms causing them to seek medical care in emergency departments (ED). Recurrent ED visits are frequent after initial discharge. We aimed to identify the characteristics of patients with Crohn’s who tend to have recurrent visits to the ED. We created an electronic data repository of all patients with inflammatory bowel diseases who visited the ED in our tertiary medical center during the period 2012–2018. For this study, we retrieved consecutive Crohn’s patients who presented with CD-related symptoms to the ED and were eventually discharged. Patients who returned to the ED in 7 and 30 days were compared with those who did not. Overall, 2299 patients visited our ED with complaints related to Crohn’s disease exacerbation or complication. A total of 1259 (60% of the adult patients) were admitted for hospitalization. Of the 632 (33%) who were discharged from the ED, 53 (8.4%) and 110 (17.4%) re-visited the ED, in 7 and 30 days from discharge, respectively. In multivariable analysis, tachycardia (odds ratio (OR) = 2.19, 95% confidence interval (CI): 1.11–4.33, p value = 0.02), elevated alkaline phosphatase (OR = 2.09, 95% CI: 1.07–4.07, p value = 0.02), and hyponatremia (OR = 2.52, 95% CI: 1.24–5.10, p value = 0.01) were associated with revisiting the ED within 7 days. Tachycardia (OR 2.88 (95% CI 1.33–6.2)), anemia (OR 2.44 (95% CI 1.24–4.8)), and elevated alkaline phosphatase (OR 2.68 (95% CI 1.25–5.78)) were independently associated with ED returns in 30 days. Knowing these risk factors may assist in minimizing the burden of recurrent ED visits among patients with CD.