To the Editor,

The Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori (H. pylori) in Children and Adolescents recommend against a “test and treat” strategy for H. pylori infection, while recommending antimicrobial sensitivity testing and tailoring eradication therapy accordingly.¹ It is strongly recommended (with a high quality of evidence and 100% agreement) that “the initial diagnosis of H. pylori infection be performed using invasive gastric biopsy-based methods including the following: a. positive bacterial culture OR b. H. pylori gastritis on histopathology using the updated Sydney classification with at least 1 other positive test such as rapid urease test, or molecular-based assays where available, including polymerase chain reaction or fluorescent in situ hybridization”.¹ However, in the new healthcare scenario emerged during the novel coronavirus disease (COVID-19) pandemic, elective pediatric diagnostic endoscopy has been substantially suspended, except for emergency cases,^{2, 3} with a minimization of the total number of procedures. As the diagnosis of H. pylori could hardly represent an emergency, unless in the cases of a bleeding ulcer, many children could remain undiagnosed for a long time and, therefore, untreated in the absence of antimicrobial sensitivity to guide the eradication strategy. To face this temporary difficulty in performing upper gastrointestinal endoscopy, a more extensive biopsy-sparing approach has been recently proposed for the diagnosis of celiac disease,⁴ considering a temporary reduction in the threshold of TGA-IgA between 5 and 10 ULN in EMA-positive children. Similarly, we would like to bring to your attention the feasibility of a temporary biopsy-sparing approach for the diagnosis and treatment of H. pylori infection in children and adolescents.

We suggest that, in children likely having H. pylori-associated gastritis or peptic ulcer disease on the basis of the presenting symptoms, the diagnosis of H. pylori infection might be made by non-invasive tests, either a ¹³C-urea breath test (UBT) or a stool 2-step monoclonal H. pylori antigen test, and an empiric eradication strategy could be adopted. In line with the treatment suggested by the Joint ESPGHAN/NASPGHAN Guidelines in the case of unknown clarithromycin resistance status, a therapeutic approach with high-dose proton-pump inhibitor, amoxicillin, and metronidazole or bismuth-based therapy can be attempted. In addition to the known high rate of clarithromycin resistance in Europe (25% in the pediatric population),⁵ it is possible that primary resistance to clarithromycin could become even higher due to the widespread use of another macrolide antibiotic, azithromycin, in some therapeutic lines for COVID-19.⁶ Undoubtedly, eradication should be assessed at least 4 weeks after completion of therapy by either a ¹³C-UBT or a stool 2-step monoclonal H. pylori antigen test, as suggested by the Joint ESPGHAN/NASPGHAN guidelines,¹ and upper gastrointestinal endoscopy should be considered in case of eradication failure or persisting symptoms. We understand that this approach is far from the gold standard management recommended by the existing guidelines, but in this critical period in which the priorities have been necessarily revised, a temporary exception might be considered, only in the areas where strict adherence to the guidelines would be more harmful than beneficial, leaving symptomatic children untreated for a long time. This exception to the current guidelines may also be considered for high risk, low-income populations, for whom the pretest probability is higher and the upper endoscopy with anesthesia is an obstacle.

致编辑，

ESPGHAN/NASPGHAN儿童和青少年幽门螺杆菌( H. pylori ) 管理联合指南建议不要对H. pylori感染采取“检测和治疗”策略，同时建议进行抗菌药物敏感性检测并相应地调整根除治疗。¹强烈建议（具有高质量证据和 100% 同意）“幽门螺杆菌感染的初步诊断应使用基于侵入性胃活检的方法进行，包括以下方法：细菌培养阳性或 b. 幽门螺杆菌胃炎的组织病理学使用更新的悉尼分类，至少有 1 项其他阳性测试，例如快速脲酶测试，或可用的基于分子的测定，包括聚合酶链反应或荧光原位杂交”。¹然而，在新型冠状病毒病 (COVID-19) 大流行期间出现的新医疗保健情景中，选择性儿科诊断内窥镜检查已基本暂停，但急诊病例除外^2、3并最大限度地减少了手术总数。作为幽门螺杆菌的诊断几乎不能代表紧急情况，除非在出血性溃疡的情况下，许多儿童可能长时间未被诊断，因此在缺乏抗菌药物敏感性来指导根除策略的情况下未经治疗。为了应对上消化道内窥镜检查的暂时困难，最近提出了一种更广泛的活检保留方法来诊断乳糜泻，⁴考虑到 EMA 阳性患者的 TGA-IgA 阈值暂时降低到 5 到 10 ULN孩子们。同样，我们想提请您注意临时保留活检方法用于诊断和治疗儿童和青少年幽门螺杆菌感染的可行性。

我们建议，对于可能患有H. pylori相关性胃炎或消化性溃疡病的儿童，根据出现的症状，H. pylori感染的诊断可通过非侵入性测试进行，即¹³ C-尿素呼气测试(UBT) 或粪便 2 步单克隆H. pylori抗原检测，以及经验性根除策略。根据 ESPGHAN/NASPGHAN 联合指南在克拉霉素耐药状态未知的情况下建议的治疗方法，可以尝试采用大剂量质子泵抑制剂、阿莫西林、甲硝唑或铋剂为基础的治疗方法。除了已知的欧洲克拉霉素耐药率高（儿科人群中为 25%）外，⁵由于另一种大环内酯类抗生素阿奇霉素在 COVID-19 的某些治疗线中的广泛使用，对克拉霉素的原发性耐药性可能会变得更高。⁶毫无疑问，应在治疗完成后至少 4 周通过¹³ C-UBT 或粪便 2 步单克隆幽门螺杆菌抗原检测评估根除情况，正如 ESPGHAN/NASPGHAN 联合指南 1 所建议的那样， ¹如果根除失败或症状持续存在，应考虑上消化道内镜检查。我们理解这种方法与现有指南推荐的黄金标准管理相去甚远，但在这个必须修改优先事项的关键时期，可能会考虑临时例外，只有在严格遵守指南的领域才会考虑弊大于利，使有症状的儿童长期得不到治疗。当前指南的这一例外情况也可考虑用于高风险、低收入人群，对他们来说，预检概率较高且上消化道内镜麻醉是一个障碍。