Behçet's Disease Masked by Appendicitis: A Case Report of a 12-Year-Old Child

Behçet's Disease Masked by Appendicitis: A Case Report of a 12-Year-Old Child | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Behçet's Disease Masked by Appendicitis: A Case Report of a 12-Year-Old Child Yi Shi, Yi-fan Ren, Yan-die Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9194540/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background: Chronic multisystem vasculitis, Behçet’s disease (BD), is characterized by relapsing autoinflammatory episodes that affect multiple body systems and organs. Although they have diverse clinical manifestations, their clinical signs and laboratory indicators lack specificity. However, the involvement of the gastrointestinal tract might make it difficult to distinguish between conditions such as appendicitis and inflammatory bowel disease. Methods: We reviewed the case of a 12-year-old girl who was initially diagnosed with “acute suppurative appendicitis” and underwent “appendectomy.” The patient experienced recurrent fever and abdominal pain postoperatively. Because the patient had recurrent oral ulcers, genital ulcers, and skin rashes and a positive pathergy test result, a final diagnosis of BD was made. We also reviewed the relevant literature to summarize and analyze this case. Conclusion: The early clinical manifestations of BD in children are frequently insufficient and easily overlooked. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/. Appendicitis Behçet’s disease Oral ulcers Genital ulcer Crohn’s disease Pathergy test Figures Figure 1 Figure 2 Introduction Behçet's disease (BD) is an autoinflammatory multisystem vasculitis characterized by recurrent episodes and remission. Recurrent oral ulcers, genital ulcers, uveitis, and skin lesions are the primary symptoms. Additionally, it might affect peripheral blood vessels, the heart, the nervous system, the gastrointestinal tract, joints, and other organs. Its incidence differs regionally; higher prevalence rates are observed in the Middle East, Far East, and Mediterranean regions. 1 – 3 In China, the incidence rate is about 14 per 100,000 individuals. 4 Symptoms often appear earlier in young adults. Although its clinical presentation is diverse, both physical signs and laboratory indicators lack specificity. Only 7–14% of such patients are diagnosed before the age of 16. 2,5 Although its precise etiology is unknown, emerging evidence suggests that it might involve genetically susceptible individuals who are exposed to triggering factors and initiate an immune-mediated process. Notably, gastrointestinal involvement is associated with a particularly poor prognosis and a high mortality rate. 5 – 7 Moreover, gastrointestinal involvement is more common in children than in adults (4–40% vs. 2–12%). 8 Therefore, enhanced clinical vigilance is warranted for patients with BD. Case Report We reviewed the case of a 12-year-old girl who initially complained of abdominal pain and fever for ten days. Physical examination revealed fixed tenderness in the right lower abdomen. Laboratory test findings revealed marked leukocytosis (20.1 × 10 9 /L, predominantly a neutrophilic shift; normal range 4.6–11.9 × 10 9 /L) and a high-sensitivity C-reactive protein concentration of 75.3 mg/L (normal value < 6 mg/L). Subsequent ultrasound revealed a strip-like hypoechoic area in the right lower abdomen, and a non- contrast CT scan of the whole abdomen demonstrated distal appendix hypertrophy, ileocecal wall thickening, and enlarged surrounding lymph nodes (Fig. 1 ). After admission to the surgical ward with acute suppurative appendicitis, she underwent a laparoscopic appendectomy. Pathology revealed extensive hemorrhage, enhanced neutrophil infiltration, and edema in the appendix and surrounding tissues. Histopathological examination revealed transmural neutrophilic infiltration with luminal purulent exudate, pathognomonic of acute suppurative appendicitis, and periappendicitis. The patient was administered postoperative combined antibiotic therapy. However, the fever and abdominal pain symptoms of the child recurred without any decrease in the leukocyte count or high-sensitivity C-reactive protein level. The erythrocyte sedimentation rate (ESR) peaked at 71 mm/h (normal value < 20 mm/h), and the hemoglobin concentration was 95 g/L (normal range 121–158 g/L). Multiple oral ulcers were observed. However, the child had experienced recurrent oral ulcers during the past year, which had self-resolved and were not considered significant. Apart from papular rashes on the lower limbs and face, she complained of diarrhea, with 3–4 episodes of yellow, loose stools daily. She was subsequently transferred to the rheumatology and immunology department for specialized care. During treatment, perineal ulcers, bloody streaks in the stool, strongly positive fecal occult blood, and a positive pathergy test were noted. Her fecal calprotectin concentration was elevated to 547.82 µg/g (normal value < 100 µg/g), and she did not respond well to anti-infection therapy. Furthermore, the serum albumin concentration decreased to 27.5 g/L (normal range 35–50 g/L), and the D-dimer concentration peaked at 1.86 mg/L (normal value < 0.5 mg/L). However, the results of the rheumatoid factor, antinuclear antibody, anti-streptolysin O, immunoglobulin, procalcitonin, cardiac ultrasound, vascular ultrasound, and non-contrast chest CT scans were normal, and no significant relevant family history was noted. Although the CD1 (Cluster of Differentiation 1) level decreased, the CD3 (Cluster of Differentiation 3), CD4 (Cluster of Differentiation 4), IL-4 (Interleukin-4), IL-6 (Interleukin-6), and IL-10 (Interleukin-10) concentrations increased. After both the adult (ICBD) and the pediatric (PEDBD) diagnostic frameworks were applied, 9,10 the patient was ultimately diagnosed with BD. Initially, she was administered intravenous immunoglobulin, anti-infection therapy, and oral and perineal care. These measures slightly improved fever and abdominal pain. However, hematochezia persisted. She was subsequently treated with infliximab, glucocorticoids, methotrexate, and cyclophosphamide, which resulted in symptom relief. After discharge, the patient received infliximab injections every four weeks. Following the third dose of infliximab, the patient experienced a type I hypersensitivity reaction. She experienced dizziness, chest tightness, shortness of breath, difficulty breathing, tachycardia, facial flushing, and cold and clammy extremities 15 min after infusion. The infusion was stopped, and symptomatic management improved the situation. Subcutaneous adalimumab (40 mg) was subsequently administered twice weekly. She achieved clinical remission at the 6-month follow-up, with no perianal lesions or involvement of the joints, heart, or nervous system. Bone marrow examination revealed the absence of myelodysplastic syndrome (MDS). Moreover, no recurrence was observed during the four-year follow-up period. During the treatment period, the child underwent regular growth and development tests, and no significant inhibition was observed. It has a positive effect on the short-term and long-term developmental and psychosocial aspects of patients. Discussion BD is a chronic immune-mediated vasculitis involving mucocutaneous tissues, eyes, blood vessels, joints, the nervous system, the gastrointestinal tract, the genitourinary system, lungs, and the heart. It is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Some patients might experience non-specific clinical manifestations such as fever, fatigue, sleep disturbances, and weight loss. 2 , 7 The BD incidence in China differs regionally, peaking at 14/100,000 in the Yangtze River Delta region. 4 The peak incidence is observed from 20 to 40 years; however, 4–26% of patients develop the disease before reaching 16 years of age. However, the clinical manifestations in children are insufficient, with a relapsing-remitting course. Given that research on pediatric BD is limited, pediatric patients take more time to develop the full disease phenotype, which makes diagnosis challenging. 11 , 12 Although its etiology is complex, it stems from interactions among innate immunity, genetic background, infectious mechanisms, environmental factors, and other factors. Moreover, a strong association was observed between the major histocompatibility complex (MHC) alleles HLA-B51 and BD. Genetic factors, such as polymorphisms in the ERAP1 risk locus, increased T-helper 17 cells, and regulatory T-cell downregulation, might increase the risk of developing BD. 5,11,13 The involvement of both large and small arteries, as well as veins, causes multisystem manifestations. 6 Oral ulcers are the initial manifestation in > 70% of BD patients, 14 with a prevalence rate as high as 99.5%, followed by genital ulcers, which occur in about 77.1% of cases. 15 The average time from the initial symptom onset to the appearance of other relevant symptoms is 6–7 years. However, oral ulcers can occur anywhere in the oral cavity and can appear as single or multiple round or oval lesions, with well-defined edges and varying depths. Usually, covered with a yellow base, they are encircled by a hemorrhagic border and heal spontaneously within 1–2 weeks without scarring. Furthermore, genital ulcers and skin lesions frequently appear at puberty. 16 Resembling oral ulcers are deeper, larger, and more painful and have a prolonged healing time. In females, they occur in the vulva, vagina, or cervix, whereas they occur in the scrotum, penis, or perianal region in males. Given that genital ulcers are extremely painful and have a prolonged healing time, they significantly impact patients' daily lives. Skin lesions are highly prevalent, occurring in 80–98% of cases. They manifest clinically as erythema nodosum, pustules, papules, acne-like rashes, or erythema multiforme. 11 BD is a distinct form of vasculitis, with fundamental pathological features encompassing varying degrees of inflammation of arteries and veins of all sizes. Thus, early diagnosis is crucial for improving quality of life and reducing mortality and morbidity. 12 Oral ulcers are relatively common in clinical practice and have various causes, and their own causes of healing are diverse. On the basis of only the symptoms of oral ulcers and the patient’s previous good health, it is difficult for us to identify patients with Behcet’s disease. The initial symptoms of Behcet's disease usually take several years to develop into other related symptoms and be diagnosed clearly. In clinical practice, pediatricians should enhance their understanding of Behcet's disease, especially for patients who initially visit departments other than rheumatology and who present with oral ulcers, abdominal pain, diarrhea, rashes, arthritis or eye diseases. Compared with that in Middle Eastern countries, the frequency of vascular and ocular lesions is lower, and gastrointestinal involvement is predominant (about 20.7%) in China. 15 Pediatric BD patients have a lower incidence of thrombocytopenia than adults. However, they predominantly exhibit folliculitis, left eye uveitis, intestinal ulcer complications, pericarditis, and psychiatric disorders. Gastrointestinal involvement in pediatric BD patients is 33.1%, making it the most frequently affected organ. 11 , 17 With a higher recurrence rate, about one-third of patients with gastrointestinal involvement eventually require surgery because of perforation, severe bleeding, obstruction, or the presence of a fistula. 18 The cumulative probability of surgery > 10 years is about 50%; however, the postoperative recurrence rate is 46.1%. 19 Moreover, delayed diagnosis and treatment can lead to poor prognosis and severe complications such as perforation, severe gastrointestinal bleeding, septic shock, and concurrent malignancies. Given that these factors significantly increase mortality, timely diagnosis and treatment of BD are crucial. This case highlights the diagnostic challenges of recognizing pediatric BD cases, particularly in the early stages. Owing to overlapping clinical features, such as fever, increased inflammatory markers, intestinal wall thickening, and abdominal pain, our patient initially complained of symptoms resembling acute appendicitis, a common misdiagnosis in pediatric BD cases. Despite suitable surgical and antibiotic interventions, the symptoms recurred and showed other systemic manifestations (Fig. 2 ), prompting diagnostic assessment. During the active phase, non-specific markers such as elevated ESR, increased C-reactive protein, hypoalbuminemia, and anemia further support the diagnosis of autoimmune disease. 11 However, an elevated level of fecal calprotectin can be used to assess disease activity in BD patients but cannot be used to differentiate this disease from Crohn's disease (CD). Thus, distinguishing between BD and CD is a challenging clinical issue because these conditions share overlapping clinical, endoscopic, and pathological features and require different therapies. BD is frequently characterized by oral and genital ulcers, ocular lesions, skin lesions, and positive pathergy test results. However, gastrointestinal involvement in BD is observed in the ileocecal region, with deep, well-defined ulcers, vasculitis, and the absence of granulomas. Perianal fistulas are less common in BD patients. Conversely, CD patients display perianal lesions, segmental distribution of the disease, longitudinal ulcers, strictures, and fistulas, along with non-caseating granulomas on pathology. Moreover, the degree of bowel wall thickening and enhancement was milder in patients with BD than in those with CD. Nonetheless, the mesenteric side of the bowel wall is often more severely affected than the anti-mesenteric side in CD patients. 3 , 20 BD responds well to corticosteroids and immunosuppressants, whereas CD often requires biologics or surgery. Thus, accurate differentiation is crucial for tailoring appropriate therapeutic strategies. With advancements in genome-wide association studies (GWAS), the detection of human leukocyte antigen (HLA)-B51 alleles has shown diagnostic value for intestinal BD. 5,21 Additionally, single-nucleotide polymorphisms (SNPs) in interleukin-23 receptor (IL-23R), interleukin-12 receptor subunit beta-2 (IL-12RB2), and interleukin-10 (IL-10) have been reported as susceptibility genes for BD. 17 Thus, these genetic insights can contribute to a better understanding of BD pathogenesis and help in timely diagnosis as well as personalized treatment approaches. Currently, intestinal ultrasound (IUS) helps in the assessment and follow-up of inflammatory bowel disease (IBD) because of its non-invasive nature, lack of radiation exposure, and cost-effectiveness in many countries. 20 Hence, IUS could be extensively utilized for the initial evaluation of gastrointestinal involvement in BD, offering a practical and efficient diagnostic tool for monitoring its activity and guiding treatment decisions. Additionally, oral ulcers indirectly reflect the severity of BD progression. In BD patients with uveitis, the combination of oral ulcers with biomarkers such as triglycerides (TG), low-density lipoprotein (LDL), and serum amyloid A (SAA) can predict recurrence risk. 22 Hence, more studies are needed to explore additional laboratory indicators and their potential association with recurrence risk in patients with BD. Currently, there is no universally recognized cure for BD. The primary treatment goals include rapidly suppressing inflammation, preventing recurrence, avoiding irreversible organ damage, and slowing disease progression. 3 The therapeutic options include glucocorticoids, colchicine, azathioprine, cyclophosphamide, anti-tumor necrosis factor (TNF)-α agents, and interferon-α. 23 The safety profiles of TNF inhibitors (such as adalimumab and infliximab) have been established, and these compounds can treat other conditions well. They are strongly recommended for refractory and/or severely affected patients requiring rapid inflammation control, as they can significantly manage disease activity, reduce complications, and reduce the need for surgery. 7 , 18 , 24 , 25 A study by Aksoy A. revealed that compared with TNF-α inhibitor monotherapy, combining TNF-α inhibitors with immunosuppressants in refractory vascular BD leads to higher complete remission rates and prolonged drug survival. 26 However, a few refractory patients still experience inadequate response, loss of efficacy, intolerance, or contraindications, 23 highlighting the need for other therapeutic agents. Vedolizumab has been proven effective for gastrointestinal-associated BD, but larger cohort studies and longer follow-up periods are needed for validation. 27 Tofacitinib (TOF) is used to treat autoinflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. 28 Although data on pediatric patients remain limited, many patients with refractory intestinal Behçet's syndrome have been treated with tofacitinib. 29 Apremilast has demonstrated efficacy in treating oral and genital ulcers in BD patients, 14,30–33 as well as in managing refractory joint and mucocutaneous manifestations; however, long-term treatment experience and pediatric data are lacking. In addition, its gastrointestinal side effects also call into question its suitability for gastrointestinal BD, warranting further research. Secukinumab has been clinically used in patients aged ≥ 6 years for psoriasis, ankylosing spondylitis, and adult BD, 21 but data on its use in pediatric BD are limited. Tocilizumab (TCZ) is now considered a promising option for refractory ocular, neurological, and vascular BD, as well as secondary amyloidosis. 23 Anti-IL-23, anti-IL-1, and anti-IL-12 agents and other biologics, such as baricitinib and calcineurin inhibitors, can be effective as new therapeutic options for refractory BD. 8,34,35 Additionally, a butyrate-rich diet can improve redox status and fibrinolysis in BD patients. 36 Since most of the studies are based on adult populations, additional research is needed to consider the growth and developmental characteristics of such pediatric cases. Owing to recent advancements in immunogenetics, syndrome recognition, and targeted therapies, the treatment of BD has improved substantially. However, the management of pediatric BD relies on adult study-based recommendations. 16 Thus, a multidisciplinary approach, personalized treatment, and early intervention are essential. Treatment plans should be tailored to the patient’s age, sex, type, and severity of organ involvement as well as other individual factors. This can ensure that they are aligned with the unique characteristics and potential adverse effects of BD in children. Limitation In the present case, the child was diagnosed with BD and had significant gastrointestinal symptoms. Unfortunately, the child refused colonoscopy, making it more directly differentiated from inflammatory bowel disease. We noted that the child experienced periorbital pain during the outpatient follow-up; however, no records of ocular examinations were available. Owing to personal reasons, HLA-B51 and related gene testing were not performed, and images of clinical manifestations at that time were not available. The child experienced sustained drug-free remission (DFR) for 48 months after treatment. To date, no similar medical history has been reported in the family. However, long-term follow-up of our patient and her family is necessary to assess the risk of recurrence, the potential involvement of other body systems, and the possibility of familial inheritance. Conclusion BD is a rare condition with an increasing incidence. Owing to the paucity of specific clinical manifestations, biomarkers, or histopathological features, its diagnosis relies primarily on the physician's individual experience, despite the relevant classification criteria. Early diagnosis and intervention are crucial for preventing disease progression and complications. Thus, our case study might increase awareness of BD, particularly in patients with oral ulcers, abdominal pain, diarrhea, skin rashes, arthritis, or eye disease who initially approach non-rheumatology departments, thereby reducing delays in diagnosis and treatment. Additional research is needed to better understand its pathogenesis, develop improved diagnostic tools and disease activity markers, and to develop more effective, safer, and personalized treatment options. Abbreviations BD Behçet's disease ESR Erythrocyte sedimentation rate CD1 Cluster of Differentiation 1 CD3 Cluster of Differentiation 3 CD4 Cluster of Differentiation 4 IL-4 Interleukin-4 IL-6 Interleukin-6 IL-10 Interleukin-10 ICBD International Criteria for Behçet‘s Disease PEDBD Pediatric Behçet‘s Disease MDS Myelodysplastic syndrome MHC Major histocompatibility complex CD Crohn's disease GWAS Genome-wide association studies SNPs Single nucleotide polymorphisms IL-23R Interleukin-23 receptor IL-12RB2 Interleukin-12 receptor subunit beta-2 IL-10 Interleukin-10 IUS Intestinal ultrasound TG Triglycerides LDL Low-density lipoprotein SAA Serum amyloid A TOF Tofacitinib TCZ Tocilizumab Declarations Acknowledgements We appreciate the patients’approval for sharing their stories and all research staff’s efforts in this study. Authors’ contributions Data collection and material preparation were performed by all authors. LYD and RYF analyzed and interpreted the patient data. First draft of the manuscript was written by SY. All authors read and approved the final manuscript. Funding The authors received no specific funding for this work. Clinical trial registration Not applicable. Data availability The datasets analyzed during the current study are available from the corresponding author on reasonable request. Ethics Approval Ethical approval for the study was granted and the case details were approved to publish the case details by ShaoXing KeQiao Women and Children’s Hospital. Consent fo r Publication Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images. A copy of the written consent form was available for review. Disclosure The authors report no conflicts of interest in this work. References Adeeb F, Dorris ER, Morgan NE, et al. A novel RELA truncating mutation in a familial behçet’s disease–like mucocutaneous ulcerative condition. 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Clin Exp Rheumatol . 2021;39(Suppl 132):80-87. doi:10.55563/clinexprheumatol/ra8ize Takeno M. Positioning of apremilast in treatment of Behçet’s disease. Mod Rheumatol . 2020;30(2):219-224. doi:10.1080/14397595.2019.1696504 Liu Y, Gao F, Yang D, Jiao Y. Intestinal Behçet's disease: A review of clinical diagnosis and treatment. World J Gastrointest Surg . 2024;16(6):1493. doi:10.4240/wjgs.v16.i6.1493 He K, Yan X, Wu D. Intestinal Behcet’s disease: a review of the immune mechanism and present and potential biological agents. Int J Mol Sci . 2023;24(9):8176. doi:10.3390/ijms24098176 Emmi G, Bettiol A, Niccolai E, et al. Butyrate-rich diets improve redox status and fibrin lysis in Behçet’s syndrome. Circ Res . 2021;128(2):278-280. doi:10.1161/CIRCRESAHA.120.317789 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 14 May, 2026 Reviewers agreed at journal 07 May, 2026 Reviewers agreed at journal 06 May, 2026 Reviewers invited by journal 06 May, 2026 Editor invited by journal 25 Mar, 2026 Editor assigned by journal 24 Mar, 2026 Submission checks completed at journal 24 Mar, 2026 First submitted to journal 22 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9194540","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":639902321,"identity":"62817bdb-520c-4bbd-ad39-6bca2bc228bb","order_by":0,"name":"Yi Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYDACCcYGhgQDCR42ZuaDDxIqaojVUmAhw8/elmzw4MwxYrSAiA8VNpI9Z8wkH7YwE9YhP7u5TeIB0GEGNxLMKhIb2Bj427sT8GoxuHOwTSIBoiXtRuIOGQaJM2c34NcikQjXcuxG4hk2oEgufi3yM+BaEtsKEtuYCWthuAHVItlzmI2BKC1Aw5stQFqAgcwskXDmGA9Bv8jPSH9488efOns2Zv6PH39U1Mjxt/cScBgDA4sEMo+HkHIQYP5AjKpRMApGwSgYwQAAVA9I21fHGNMAAAAASUVORK5CYII=","orcid":"","institution":"Shaoxing Keqiao Women And Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yi","middleName":"","lastName":"Shi","suffix":""},{"id":639902323,"identity":"559678f3-f1d5-44e8-8695-9fc82d4ca23a","order_by":1,"name":"Yi-fan Ren","email":"","orcid":"","institution":"Shaoxing Keqiao Women And Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-fan","middleName":"","lastName":"Ren","suffix":""},{"id":639902325,"identity":"7abc7c7e-5aee-4466-be52-4e13214d9c37","order_by":2,"name":"Yan-die Li","email":"","orcid":"","institution":"Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,","correspondingAuthor":false,"prefix":"","firstName":"Yan-die","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-03-23 02:08:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9194540/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9194540/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109302591,"identity":"002a5a66-5d01-4160-afdc-09e11906f6b1","added_by":"auto","created_at":"2026-05-15 09:37:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":402942,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative CT scan of the appendix revealed the absence of thickening of the ileocecal bowel wall and surrounding mesenteric lymph node.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9194540/v1/f6bb4923a0519efc826b6b9c.png"},{"id":109405403,"identity":"0a9a8709-6f8a-414a-a70c-00dca5132058","added_by":"auto","created_at":"2026-05-17 13:17:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":225208,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment: A: antibiotics (intravenous combination antibiotic therapy for the treatment of infections);\u003c/p\u003e\n\u003cp\u003eS: surgical removal of the appendix (laparoscopic appendectomy);\u003c/p\u003e\n\u003cp\u003eI1: Immunoglobulin (human immune gamma globulin 20 g per dose, twice, administered intravenously);\u003c/p\u003e\n\u003cp\u003eI2: Infliximab (Remicade, 200 mg per dose, administered intravenously);\u003c/p\u003e\n\u003cp\u003eG: Glucocorticoids (methylprednisolone 20 mg per dose, twice daily, administered intravenously (10/14–10/21)); methylprednisolone 20 mg per dose, once daily, administered intravenously (10/14–10/21); prednisone acetate tablets 25 mg per dose, once daily, taken orally (10/22–10/25).\u003c/p\u003e\n\u003cp\u003eM: methotrexate (MTX; 10 mg per dose, once weekly, taken orally).\u003c/p\u003e\n\u003cp\u003eNotes: The data in this table include only the period from one day before the child's surgery to the day of discharge. The colored bar chart indicates that the child has symptoms. The date format is month/day.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9194540/v1/ea6e6b62b24908cf8b5fd145.png"},{"id":109406104,"identity":"ca3dd6e3-c312-409b-be6d-a525f5255e11","added_by":"auto","created_at":"2026-05-17 13:24:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":830284,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9194540/v1/fdca899c-e7c5-4436-9ea6-832a85a63b6e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Behçet's Disease Masked by Appendicitis: A Case Report of a 12-Year-Old Child","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBeh\u0026ccedil;et's disease (BD) is an autoinflammatory multisystem vasculitis characterized by recurrent episodes and remission. Recurrent oral ulcers, genital ulcers, uveitis, and skin lesions are the primary symptoms. Additionally, it might affect peripheral blood vessels, the heart, the nervous system, the gastrointestinal tract, joints, and other organs. Its incidence differs regionally; higher prevalence rates are observed in the Middle East, Far East, and Mediterranean regions.\u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e In China, the incidence rate is about 14 per 100,000 individuals.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Symptoms often appear earlier in young adults. Although its clinical presentation is diverse, both physical signs and laboratory indicators lack specificity. Only 7\u0026ndash;14% of such patients are diagnosed before the age of 16.\u003csup\u003e2,5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough its precise etiology is unknown, emerging evidence suggests that it might involve genetically susceptible individuals who are exposed to triggering factors and initiate an immune-mediated process. Notably, gastrointestinal involvement is associated with a particularly poor prognosis and a high mortality rate.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Moreover, gastrointestinal involvement is more common in children than in adults (4\u0026ndash;40% vs. 2\u0026ndash;12%).\u003csup\u003e8\u003c/sup\u003e Therefore, enhanced clinical vigilance is warranted for patients with BD.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eWe reviewed the case of a 12-year-old girl who initially complained of abdominal pain and fever for ten days. Physical examination revealed fixed tenderness in the right lower abdomen. Laboratory test findings revealed marked leukocytosis (20.1 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, predominantly a neutrophilic shift; normal range 4.6\u0026ndash;11.9 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L) and a high-sensitivity C-reactive protein concentration of 75.3 mg/L (normal value\u0026thinsp;\u0026lt;\u0026thinsp;6 mg/L). Subsequent ultrasound revealed a strip-like hypoechoic area in the right lower abdomen, and a non-\u003cb\u003econtrast\u003c/b\u003e CT scan of the whole abdomen demonstrated distal appendix hypertrophy, ileocecal wall thickening, and enlarged surrounding lymph nodes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). After admission to the surgical ward with acute suppurative appendicitis, she underwent a laparoscopic appendectomy. Pathology revealed extensive hemorrhage, enhanced neutrophil infiltration, and edema in the appendix and surrounding tissues. Histopathological examination revealed transmural neutrophilic infiltration with luminal purulent exudate, pathognomonic of acute suppurative appendicitis, and periappendicitis. The patient was administered postoperative combined antibiotic therapy. However, the fever and abdominal pain symptoms of the child recurred without any decrease in the leukocyte count or high-sensitivity C-reactive protein level. The erythrocyte sedimentation rate (ESR) peaked at 71 mm/h (normal value\u0026thinsp;\u0026lt;\u0026thinsp;20 mm/h), and the hemoglobin concentration was 95 g/L (normal range 121\u0026ndash;158 g/L). Multiple oral ulcers were observed. However, the child had experienced recurrent oral ulcers during the past year, which had self-resolved and were not considered significant. Apart from papular rashes on the lower limbs and face, she complained of diarrhea, with 3\u0026ndash;4 episodes of yellow, loose stools daily. She was subsequently transferred to the rheumatology and immunology department for specialized care. During treatment, perineal ulcers, bloody streaks in the stool, strongly positive fecal occult blood, and a positive pathergy test were noted. Her fecal calprotectin concentration was elevated to 547.82 \u0026micro;g/g (normal value\u0026thinsp;\u0026lt;\u0026thinsp;100 \u0026micro;g/g), and she did not respond well to anti-infection therapy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, the serum albumin concentration decreased to 27.5 g/L (normal range 35\u0026ndash;50 g/L), and the D-dimer concentration peaked at 1.86 mg/L (normal value\u0026thinsp;\u0026lt;\u0026thinsp;0.5 mg/L). However, the results of the rheumatoid factor, antinuclear antibody, anti-streptolysin O, immunoglobulin, procalcitonin, cardiac ultrasound, vascular ultrasound, and non-contrast chest CT scans were normal, and no significant relevant family history was noted. Although the CD1 (Cluster of Differentiation 1) level decreased, the CD3 (Cluster of Differentiation 3), CD4 (Cluster of Differentiation 4), IL-4 (Interleukin-4), IL-6 (Interleukin-6), and IL-10 (Interleukin-10) concentrations increased.\u003c/p\u003e \u003cp\u003eAfter both the adult (ICBD) and the pediatric (PEDBD) diagnostic frameworks were applied,\u003csup\u003e9,10\u003c/sup\u003e the patient was ultimately diagnosed with BD. Initially, she was administered intravenous immunoglobulin, anti-infection therapy, and oral and perineal care. These measures slightly improved fever and abdominal pain. However, hematochezia persisted. She was subsequently treated with infliximab, glucocorticoids, methotrexate, and cyclophosphamide, which resulted in symptom relief. After discharge, the patient received infliximab injections every four weeks. Following the third dose of infliximab, the patient experienced a type I hypersensitivity reaction. She experienced dizziness, chest tightness, shortness of breath, difficulty breathing, tachycardia, facial flushing, and cold and clammy extremities 15 min after infusion. The infusion was stopped, and symptomatic management improved the situation. Subcutaneous adalimumab (40 mg) was subsequently administered twice weekly. She achieved clinical remission at the 6-month follow-up, with no perianal lesions or involvement of the joints, heart, or nervous system. Bone marrow examination revealed the absence of myelodysplastic syndrome (MDS). Moreover, no recurrence was observed during the four-year follow-up period. During the treatment period, the child underwent regular growth and development tests, and no significant inhibition was observed. It has a positive effect on the short-term and long-term developmental and psychosocial aspects of patients.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBD is a chronic immune-mediated vasculitis involving mucocutaneous tissues, eyes, blood vessels, joints, the nervous system, the gastrointestinal tract, the genitourinary system, lungs, and the heart. It is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Some patients might experience non-specific clinical manifestations such as fever, fatigue, sleep disturbances, and weight loss.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The BD incidence in China differs regionally, peaking at 14/100,000 in the Yangtze River Delta region.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The peak incidence is observed from 20 to 40 years; however, 4\u0026ndash;26% of patients develop the disease before reaching 16 years of age. However, the clinical manifestations in children are insufficient, with a relapsing-remitting course. Given that research on pediatric BD is limited, pediatric patients take more time to develop the full disease phenotype, which makes diagnosis challenging.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough its etiology is complex, it stems from interactions among innate immunity, genetic background, infectious mechanisms, environmental factors, and other factors. Moreover, a strong association was observed between the major histocompatibility complex (MHC) alleles HLA-B51 and BD. Genetic factors, such as polymorphisms in the ERAP1 risk locus, increased T-helper 17 cells, and regulatory T-cell downregulation, might increase the risk of developing BD.\u003csup\u003e5,11,13\u003c/sup\u003e The involvement of both large and small arteries, as well as veins, causes multisystem manifestations.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOral ulcers are the initial manifestation in \u0026gt;\u0026thinsp;70% of BD patients,\u003csup\u003e14\u003c/sup\u003e with a prevalence rate as high as 99.5%, followed by genital ulcers, which occur in about 77.1% of cases.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e The average time from the initial symptom onset to the appearance of other relevant symptoms is 6\u0026ndash;7 years. However, oral ulcers can occur anywhere in the oral cavity and can appear as single or multiple round or oval lesions, with well-defined edges and varying depths. Usually, covered with a yellow base, they are encircled by a hemorrhagic border and heal spontaneously within 1\u0026ndash;2 weeks without scarring. Furthermore, genital ulcers and skin lesions frequently appear at puberty.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Resembling oral ulcers are deeper, larger, and more painful and have a prolonged healing time. In females, they occur in the vulva, vagina, or cervix, whereas they occur in the scrotum, penis, or perianal region in males. Given that genital ulcers are extremely painful and have a prolonged healing time, they significantly impact patients' daily lives. Skin lesions are highly prevalent, occurring in 80\u0026ndash;98% of cases. They manifest clinically as erythema nodosum, pustules, papules, acne-like rashes, or erythema multiforme.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e BD is a distinct form of vasculitis, with fundamental pathological features encompassing varying degrees of inflammation of arteries and veins of all sizes. Thus, early diagnosis is crucial for improving quality of life and reducing mortality and morbidity.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOral ulcers are relatively common in clinical practice and have various causes, and their own causes of healing are diverse. On the basis of only the symptoms of oral ulcers and the patient\u0026rsquo;s previous good health, it is difficult for us to identify patients with Behcet\u0026rsquo;s disease. The initial symptoms of Behcet's disease usually take several years to develop into other related symptoms and be diagnosed clearly. In clinical practice, pediatricians should enhance their understanding of Behcet's disease, especially for patients who initially visit departments other than rheumatology and who present with oral ulcers, abdominal pain, diarrhea, rashes, arthritis or eye diseases.\u003c/p\u003e \u003cp\u003eCompared with that in Middle Eastern countries, the frequency of vascular and ocular lesions is lower, and gastrointestinal involvement is predominant (about 20.7%) in China.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Pediatric BD patients have a lower incidence of thrombocytopenia than adults. However, they predominantly exhibit folliculitis, left eye uveitis, intestinal ulcer complications, pericarditis, and psychiatric disorders. Gastrointestinal involvement in pediatric BD patients is 33.1%, making it the most frequently affected organ.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e With a higher recurrence rate, about one-third of patients with gastrointestinal involvement eventually require surgery because of perforation, severe bleeding, obstruction, or the presence of a fistula.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The cumulative probability of surgery\u0026thinsp;\u0026gt;\u0026thinsp;10 years is about 50%; however, the postoperative recurrence rate is 46.1%.\u003csup\u003e19\u003c/sup\u003e Moreover, delayed diagnosis and treatment can lead to poor prognosis and severe complications such as perforation, severe gastrointestinal bleeding, septic shock, and concurrent malignancies. Given that these factors significantly increase mortality, timely diagnosis and treatment of BD are crucial.\u003c/p\u003e \u003cp\u003eThis case highlights the diagnostic challenges of recognizing pediatric BD cases, particularly in the early stages. Owing to overlapping clinical features, such as fever, increased inflammatory markers, intestinal wall thickening, and abdominal pain, our patient initially complained of symptoms resembling acute appendicitis, a common misdiagnosis in pediatric BD cases. Despite suitable surgical and antibiotic interventions, the symptoms recurred and showed other systemic manifestations (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), prompting diagnostic assessment.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDuring the active phase, non-specific markers such as elevated ESR, increased C-reactive protein, hypoalbuminemia, and anemia further support the diagnosis of autoimmune disease.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e However, an elevated level of fecal calprotectin can be used to assess disease activity in BD patients but cannot be used to differentiate this disease from Crohn's disease (CD). Thus, distinguishing between BD and CD is a challenging clinical issue because these conditions share overlapping clinical, endoscopic, and pathological features and require different therapies.\u003c/p\u003e \u003cp\u003eBD is frequently characterized by oral and genital ulcers, ocular lesions, skin lesions, and positive pathergy test results. However, gastrointestinal involvement in BD is observed in the ileocecal region, with deep, well-defined ulcers, vasculitis, and the absence of granulomas. Perianal fistulas are less common in BD patients. Conversely, CD patients display perianal lesions, segmental distribution of the disease, longitudinal ulcers, strictures, and fistulas, along with non-caseating granulomas on pathology. Moreover, the degree of bowel wall thickening and enhancement was milder in patients with BD than in those with CD. Nonetheless, the mesenteric side of the bowel wall is often more severely affected than the anti-mesenteric side in CD patients.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBD responds well to corticosteroids and immunosuppressants, whereas CD often requires biologics or surgery. Thus, accurate differentiation is crucial for tailoring appropriate therapeutic strategies.\u003c/p\u003e \u003cp\u003eWith advancements in genome-wide association studies (GWAS), the detection of human leukocyte antigen (HLA)-B51 alleles has shown diagnostic value for intestinal BD.\u003csup\u003e5,21\u003c/sup\u003e Additionally, single-nucleotide polymorphisms (SNPs) in interleukin-23 receptor (IL-23R), interleukin-12 receptor subunit beta-2 (IL-12RB2), and interleukin-10 (IL-10) have been reported as susceptibility genes for BD.\u003csup\u003e17\u003c/sup\u003e Thus, these genetic insights can contribute to a better understanding of BD pathogenesis and help in timely diagnosis as well as personalized treatment approaches.\u003c/p\u003e \u003cp\u003eCurrently, intestinal ultrasound (IUS) helps in the assessment and follow-up of inflammatory bowel disease (IBD) because of its non-invasive nature, lack of radiation exposure, and cost-effectiveness in many countries.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Hence, IUS could be extensively utilized for the initial evaluation of gastrointestinal involvement in BD, offering a practical and efficient diagnostic tool for monitoring its activity and guiding treatment decisions.\u003c/p\u003e \u003cp\u003eAdditionally, oral ulcers indirectly reflect the severity of BD progression. In BD patients with uveitis, the combination of oral ulcers with biomarkers such as triglycerides (TG), low-density lipoprotein (LDL), and serum amyloid A (SAA) can predict recurrence risk.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Hence, more studies are needed to explore additional laboratory indicators and their potential association with recurrence risk in patients with BD.\u003c/p\u003e \u003cp\u003eCurrently, there is no universally recognized cure for BD. The primary treatment goals include rapidly suppressing inflammation, preventing recurrence, avoiding irreversible organ damage, and slowing disease progression.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The therapeutic options include glucocorticoids, colchicine, azathioprine, cyclophosphamide, anti-tumor necrosis factor (TNF)-α agents, and interferon-α.\u003csup\u003e23\u003c/sup\u003e The safety profiles of TNF inhibitors (such as adalimumab and infliximab) have been established, and these compounds can treat other conditions well. They are strongly recommended for refractory and/or severely affected patients requiring rapid inflammation control, as they can significantly manage disease activity, reduce complications, and reduce the need for surgery.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e A study by Aksoy A. revealed that compared with TNF-α inhibitor monotherapy, combining TNF-α inhibitors with immunosuppressants in refractory vascular BD leads to higher complete remission rates and prolonged drug survival.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e However, a few refractory patients still experience inadequate response, loss of efficacy, intolerance, or contraindications,\u003csup\u003e23\u003c/sup\u003e highlighting the need for other therapeutic agents.\u003c/p\u003e \u003cp\u003eVedolizumab has been proven effective for gastrointestinal-associated BD, but larger cohort studies and longer follow-up periods are needed for validation.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Tofacitinib (TOF) is used to treat autoinflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Although data on pediatric patients remain limited, many patients with refractory intestinal Beh\u0026ccedil;et's syndrome have been treated with tofacitinib.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Apremilast has demonstrated efficacy in treating oral and genital ulcers in BD patients,\u003csup\u003e14,30\u0026ndash;33\u003c/sup\u003e as well as in managing refractory joint and mucocutaneous manifestations; however, long-term treatment experience and pediatric data are lacking. In addition, its gastrointestinal side effects also call into question its suitability for gastrointestinal BD, warranting further research. Secukinumab has been clinically used in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;6 years for psoriasis, ankylosing spondylitis, and adult BD,\u003csup\u003e21\u003c/sup\u003e but data on its use in pediatric BD are limited. Tocilizumab (TCZ) is now considered a promising option for refractory ocular, neurological, and vascular BD, as well as secondary amyloidosis.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Anti-IL-23, anti-IL-1, and anti-IL-12 agents and other biologics, such as baricitinib and calcineurin inhibitors, can be effective as new therapeutic options for refractory BD.\u003csup\u003e8,34,35\u003c/sup\u003e Additionally, a butyrate-rich diet can improve redox status and fibrinolysis in BD patients.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e Since most of the studies are based on adult populations, additional research is needed to consider the growth and developmental characteristics of such pediatric cases.\u003c/p\u003e \u003cp\u003eOwing to recent advancements in immunogenetics, syndrome recognition, and targeted therapies, the treatment of BD has improved substantially. However, the management of pediatric BD relies on adult study-based recommendations.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Thus, a multidisciplinary approach, personalized treatment, and early intervention are essential. Treatment plans should be tailored to the patient\u0026rsquo;s age, sex, type, and severity of organ involvement as well as other individual factors. This can ensure that they are aligned with the unique characteristics and potential adverse effects of BD in children.\u003c/p\u003e\n\u003ch3\u003eLimitation\u003c/h3\u003e\n\u003cp\u003eIn the present case, the child was diagnosed with BD and had significant gastrointestinal symptoms. Unfortunately, the child refused colonoscopy, making it more directly differentiated from inflammatory bowel disease. We noted that the child experienced periorbital pain during the outpatient follow-up; however, no records of ocular examinations were available. Owing to personal reasons, HLA-B51 and related gene testing were not performed, and images of clinical manifestations at that time were not available. The child experienced sustained drug-free remission (DFR) for 48 months after treatment. To date, no similar medical history has been reported in the family. However, long-term follow-up of our patient and her family is necessary to assess the risk of recurrence, the potential involvement of other body systems, and the possibility of familial inheritance.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBD is a rare condition with an increasing incidence. Owing to the paucity of specific clinical manifestations, biomarkers, or histopathological features, its diagnosis relies primarily on the physician's individual experience, despite the relevant classification criteria. Early diagnosis and intervention are crucial for preventing disease progression and complications. Thus, our case study might increase awareness of BD, particularly in patients with oral ulcers, abdominal pain, diarrhea, skin rashes, arthritis, or eye disease who initially approach non-rheumatology departments, thereby reducing delays in diagnosis and treatment. Additional research is needed to better understand its pathogenesis, develop improved diagnostic tools and disease activity markers, and to develop more effective, safer, and personalized treatment options.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eBeh\u0026ccedil;et\u0026apos;s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eESR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eErythrocyte sedimentation rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eCD1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eCluster of Differentiation 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eCD3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eCluster of Differentiation 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eCD4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eCluster of Differentiation 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eICBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInternational Criteria for Beh\u0026ccedil;et\u0026lsquo;s Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003ePEDBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003ePediatric Beh\u0026ccedil;et\u0026lsquo;s Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eMDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eMyelodysplastic syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eMHC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eMajor histocompatibility complex\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eCrohn\u0026apos;s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eGWAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eGenome-wide association studies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eSNPs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eSingle nucleotide polymorphisms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-23R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-23 receptor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-12RB2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-12 receptor subunit beta-2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIL-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eInterleukin-10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eIUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eIntestinal ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eTriglycerides\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eLDL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eLow-density lipoprotein\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eSAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eSerum amyloid A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eTOF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eTofacitinib\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 32.2034%;\"\u003e\n \u003cp\u003eTCZ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67.7966%;\"\u003e\n \u003cp\u003eTocilizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the patients\u0026rsquo;approval for sharing their stories and all research staff\u0026rsquo;s efforts in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData collection and material preparation were performed by all authors. LYD and RYF analyzed and interpreted the patient data. First draft of the manuscript was written by SY. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for the study was granted and the case details were approved to publish the case details by ShaoXing KeQiao Women and Children\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent fo\u003c/strong\u003e\u003cstrong\u003er Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient\u0026rsquo;s parents for publication of this case report and any accompanying images. A copy of the written consent form was available for review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAdeeb F, Dorris ER, Morgan NE, et al. A novel RELA truncating mutation in a familial beh\u0026ccedil;et\u0026rsquo;s disease\u0026ndash;like mucocutaneous ulcerative condition. \u003cem\u003eArthritis Rheumatol\u003c/em\u003e. 2021;73(3):490-497. doi:10.1002/art.41531\u003c/li\u003e\n \u003cli\u003eBettiol A, Prisco D, Emmi G. Beh\u0026ccedil;et: the syndrome. \u003cem\u003eRheumatology\u003c/em\u003e. 2020;59(Suppl 3):iii101-iii107. doi:10.1093/rheumatology/kez626\u003c/li\u003e\n \u003cli\u003eSaadoun D, Bodaghi B, Cacoub P. 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SER recommendations on treatment of refractory Beh\u0026ccedil;et\u0026apos;s syndrome. \u003cem\u003eReumatol Clin (Engl Ed)\u003c/em\u003e. 2024;20(4):204-217. doi:10.1016/j.reumae.2023.12.006\u003c/li\u003e\n \u003cli\u003eZou J, Cai J, Ye J, Guan J. Tofacitinib as an alternative therapy for refractory intestinal Beh\u0026ccedil;et\u0026rsquo;s syndrome. \u003cem\u003eTher Adv Musculoskelet Dis\u003c/em\u003e. 2022;14:1759720X221124014. doi:10.1177/1759720X221124014\u003c/li\u003e\n \u003cli\u003eMa L, Wang M, Li W, et al. Pilot case-control study to explore the value of intestinal ultrasound in the differentiation of two common diseases involving the ileocecal region: intestinal Beh\u0026ccedil;et\u0026rsquo;s disease and Crohn\u0026rsquo;s disease. \u003cem\u003eQuant Imaging Med Surg\u003c/em\u003e. 2021;11(7):3200-3208. doi:10.21037/qims-20-1334\u003c/li\u003e\n \u003cli\u003eFagni F, Bettiol A, Talarico R, et al. Long-term effectiveness and safety of secukinumab for treatment of refractory mucosal and articular Beh\u0026ccedil;et\u0026apos;s phenotype: a multicentre study. \u003cem\u003eAnn Rheum Dis\u003c/em\u003e. 2020;79(8):1098-1104. doi:10.1136/annrheumdis-2020-217108\u003c/li\u003e\n \u003cli\u003eCai J, Qi L, Chen Y, et al. Evaluation of factors for predicting risk of uveitis recurrence in Behcet\u0026apos;s disease patients. \u003cem\u003eBraz J Med Biol Res\u003c/em\u003e. 2020;53(6):e9118. doi:10.1590/1414-431x20209118\u003c/li\u003e\n \u003cli\u003eAkiyama M, Kaneko Y, Takeuchi T. Effectiveness of tocilizumab in Behcet\u0026apos;s disease: a systematic literature review. \u003cem\u003eSemin Arthritis Rheum\u003c/em\u003e. 2020;50:797-804. doi:10.1016/j.semarthrit.2020.05.017\u003c/li\u003e\n \u003cli\u003eSuzuki Y, Hagiwara T, Kobayashi M, Morita K, Shimamoto T, Hibi T. Long-term safety and effectiveness of adalimumab in 462 patients with intestinal Beh\u0026ccedil;et\u0026rsquo;s disease: results from a large real-world observational study. \u003cem\u003eIntest Res\u003c/em\u003e. 2021;19(3):301-312. doi:10.5217/ir.2020.00013\u003c/li\u003e\n \u003cli\u003eLiu J, Yan D, Wang Z, et al. Tocilizumab in the treatment of severe and refractory parenchymal neuro-Beh\u0026ccedil;et\u0026rsquo;s syndrome: case series and literature review. \u003cem\u003eTher Adv Musculoskelet Dis\u003c/em\u003e. 2020;12:1759720X20971908. doi:10.1177/1759720X20971908\u003c/li\u003e\n \u003cli\u003eAksoy A, Yazici A, Omma A, et al. 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Case report: refractory intestinal Beh\u0026ccedil;et\u0026rsquo;s syndrome successfully treated with tofacitinib: a report of four cases. \u003cem\u003eFront Immunol\u003c/em\u003e. 2022;13:981502. doi:10.3389/fimmu.2022.981502\u003c/li\u003e\n \u003cli\u003eAtienza-Mateo B, Mart\u0026iacute;n-Varillas JL, Gra\u0026ntilde;a J, et al. Apremilast in refractory orogenital ulcers and other manifestations of Beh\u0026ccedil;et\u0026apos;s disease. National multicenter study of 51 cases in clinical practice. \u003cem\u003eClin Exp Rheumatol\u003c/em\u003e. 2020;38(Suppl 127):69-75. doi:10.21203/rs.3.rs-25996/v1\u003c/li\u003e\n \u003cli\u003eVieira M, Buffier S, Vautier M, et al. Apremilast in refractory Beh\u0026ccedil;et\u0026rsquo;s syndrome: a multicenter observational study. \u003cem\u003eFront Immunol\u003c/em\u003e. 2021;11:626792. doi:10.3389/fimmu.2020.626792\u003c/li\u003e\n \u003cli\u003eHatemi G, Mahr A, Takeno M, et al. Apremilast for oral ulcers associated with active Beh\u0026ccedil;et\u0026rsquo;s syndrome over 68 weeks: long-term results from a phase 3 randomised clinical trial. \u003cem\u003eClin Exp Rheumatol\u003c/em\u003e. 2021;39(Suppl 132):80-87. doi:10.55563/clinexprheumatol/ra8ize\u003c/li\u003e\n \u003cli\u003eTakeno M. Positioning of apremilast in treatment of Beh\u0026ccedil;et\u0026rsquo;s disease. \u003cem\u003eMod Rheumatol\u003c/em\u003e. 2020;30(2):219-224. doi:10.1080/14397595.2019.1696504\u003c/li\u003e\n \u003cli\u003eLiu Y, Gao F, Yang D, Jiao Y. Intestinal Beh\u0026ccedil;et\u0026apos;s disease: A review of clinical diagnosis and treatment. \u003cem\u003eWorld J Gastrointest Surg\u003c/em\u003e. 2024;16(6):1493. doi:10.4240/wjgs.v16.i6.1493\u003c/li\u003e\n \u003cli\u003eHe K, Yan X, Wu D. Intestinal Behcet\u0026rsquo;s disease: a review of the immune mechanism and present and potential biological agents. \u003cem\u003eInt J Mol Sci\u003c/em\u003e. 2023;24(9):8176. doi:10.3390/ijms24098176\u003c/li\u003e\n \u003cli\u003eEmmi G, Bettiol A, Niccolai E, et al. Butyrate-rich diets improve redox status and fibrin lysis in Beh\u0026ccedil;et\u0026rsquo;s syndrome. \u003cem\u003eCirc Res\u003c/em\u003e. 2021;128(2):278-280. doi:10.1161/CIRCRESAHA.120.317789\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Appendicitis, Behçet’s disease, Oral ulcers, Genital ulcer, Crohn’s disease, Pathergy test","lastPublishedDoi":"10.21203/rs.3.rs-9194540/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9194540/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Chronic multisystem vasculitis, Behçet’s disease (BD), is characterized by relapsing autoinflammatory episodes that affect multiple body systems and organs. Although they have diverse clinical manifestations, their clinical signs and laboratory indicators lack specificity. However, the involvement of the gastrointestinal tract might make it difficult to distinguish between conditions such as appendicitis and inflammatory bowel disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We reviewed the case of a 12-year-old girl who was initially diagnosed with “acute suppurative appendicitis” and underwent “appendectomy.” The patient experienced recurrent fever and abdominal pain postoperatively. Because the patient had recurrent oral ulcers, genital ulcers, and skin rashes and a positive pathergy test result, a final diagnosis of BD was made. We also reviewed the relevant literature to summarize and analyze this case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The early clinical manifestations of BD in children are frequently insufficient and easily overlooked.\u003c/p\u003e\n\u003cp\u003eData Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/.\u003c/p\u003e","manuscriptTitle":"Behçet's Disease Masked by Appendicitis: A Case Report of a 12-Year-Old Child","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-15 09:37:41","doi":"10.21203/rs.3.rs-9194540/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-15T02:25:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12902442199656756062814354253595568446","date":"2026-05-07T14:24:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285282531879111453793217582004120828746","date":"2026-05-06T08:36:09+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-05-06T07:34:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-25T06:54:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-25T02:09:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-25T02:09:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-03-23T01:58:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c9a7ac4-f880-4d9a-92d3-46d5933d6dbd","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-15T02:25:40+00:00","index":47,"fulltext":""},{"type":"reviewerAgreed","content":"12902442199656756062814354253595568446","date":"2026-05-07T14:24:36+00:00","index":44,"fulltext":""},{"type":"reviewerAgreed","content":"285282531879111453793217582004120828746","date":"2026-05-06T08:36:09+00:00","index":42,"fulltext":""},{"type":"reviewersInvited","content":"15","date":"2026-05-06T07:34:34+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T09:37:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 09:37:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9194540","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9194540","identity":"rs-9194540","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}