Behcet's disease (BD) was first reported in 1937 by the Turkish dermatologist Hulusi Behcet. In 1941, Knapp wrote the first clinical case of neurological manifestation of BD, which was later termed Neuro-Behcet's disease (NBD) by Cavara and D'Ermo (1). BD becomes NBD upon the neurological involvement (2). NBD is relatively rare in children and difficult to diagnose, causing delayed diagnosis and treatment.

BD is a systemic inflammatory disease with clinical characteristics of autoinflammatory diseases and vasculitis (3). The main clinical features include recurrent oral ulcers, genital ulcers, and uveitis, and they can affect multiple parts of the body, such as the skin, joints, and cardiovascular, digestive, and nervous systems (4). Previous studies have shown that this condition is related to human leukocyte antigen-B51 (HLA-B51) (5). Cerebral venous sinus thrombosis (CVST) is the most common manifestation of NBD in children (6).

Maldini et al. (7) have estimated that the global prevalence of BD in adults is approximately 10.3 per 100,000 people, with different prevalence rates in different countries. The incidence rate of BD in children is unclear. Nevertheless, 4–26 % of BD cases have been reported to occur before the age of 16 years (8). The incidence of NBD in BD patients is approximately 9% (range, 3–30%) (9). The average age of NBD onset in children is around 12 years (10). Boys are more likely to develop NBD than adult men (2).

Here we report a pediatric case of NBD with intestinal lesions.

NBD in children is different from that observed in adults. It is reported in 3.6–59.6% of pediatric BD cases, and the incidence of NBD-related cerebrovascular diseases is higher in children than in adults (11, 12). Metreau-Vaste et al. (6) have found that the most common neurological lesion is CVST, whereas meningoencephalitis and peripheral neuritis are rare. In their study, two of the 12 children (17%) had abdominal pain with severe colonic ulcers. Our case also presented with abdominal pain and intestinal mucosal ulcers. Previous studies have reported that such cases are relatively rare.

It has been reported that the most common initial neurological symptoms are headache and epileptic seizure. Cranial neuropathy and hemiplegia may also occur in NBD, but the most common type of neurological involvement is CVST (2). Through MRI and MRV, CVST can be detected most prominently in transverse and superior sagittal sinuses. In a few children, the brain stem and spinal cord may be involved (2). The CVST in our case mainly occurred in the transverse and superior sagittal sinuses (Figures 4A,B).

The uveitis in the right eye, appendicitis, and perianal abscess in this case resulted from NBD. However, these symptoms may be easily ignored in clinical practice. This patient has undergone intraocular lens implantation, appendectomy, and perianal abscess removal. Abdominal pain was the main symptom in the patient. He was misdiagnosed with CD based on the colonoscopy findings.

As intestinal BD and CD share many common characteristics, including genetic factors, clinical manifestations, and courses of pathogenesis and treatment, it is difficult to distinguish between the two diseases. Some experts believe that the two diseases are simply different clinical manifestations of the same disease, but others think BD and CD are completely different diseases (12). The major differences between these two diseases are the clinical manifestations; BD results in oral and genital ulcers and involves the nervous system, occlusive vascular disease, and thrombosis, whereas patients with CD generally have anal complications, such as stenosis, abscess formation, and fistula, which are rare in BD (13). However, the perianal abscess in our case might have been easily misdiagnosed as CD. Nevertheless, colonoscopy can reveal the differences between the two diseases. BD is localized in the terminal ileum or ileocecal region and usually has single or several, discrete, large, and round or oval ulcers. The classical endoscopic appearance of CD involves discontinuous mucosal inflammation, longitudinal ulcer, and pebbly appearance of the normal surrounding mucosa. In our patient, the presentation was concentrated in the ileocecal region (Figures 1A,B), more in line with BD than CD. The pathological manifestations of CD are cryptitis and non-caseous granuloma, whereas those of BD are vasculitis, mucosal inflammation, with/without ulcerative (12, 14). Pathologically, the patient had changes in the crypts (Figures 2A,B), similar to those seen in CD. Moreover, CD has been reported with extensive thrombosis in the limbs and CVST (15–19). A study has reported that the thrombosis prevalence among patients with CD is 5.7% (20). In addition, BD is frequently misdiagnosed as CD in adults (21). Overall, CD has many features that overlap with BD, and as our case shows, distinguishing between these two conditions can be challenging.

Therefore, the patient was initially diagnosed with CD because of its clinical presentation. For children, CD can be distinguished from BD when the disease is accompanied by oral ulcers, and the colonoscopic lesions are limited to the ileocecal area (round and oval ulcers). Pathological and parenteral manifestations should be considered, and the diagnosis should be made after reviewing the history again. Furthermore, the MRI of the head or MRV may be considered. If CVST is detected, NBD can be diagnosed.

The therapeutic goal of NBD is to inhibit the progression and recurrence of inflammation to prevent irreversible organ damage. The first-line drugs against NBD are high-dose glucocorticoids, cyclophosphamide, and azathioprine, whereas refractory NBD can be treated with second-line drugs, such as anti-tumor necrosis factor (TNF)-α or tocilizumab (14). However, additional reliable evidence is still needed to prove the efficacy and safety of biologics in the treatment of pediatric NBD.

In conclusion, NBD is prone to misdiagnosis and missed diagnosis and should be diagnosed based on clinical manifestations and results from colonoscopy, pathological examination, and MRI or MRV.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Ethics Committee of Shenzhen Children's Hospital. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.

QZ and ZW: conceptualization and writing original draft. YL and JZ: data collection. QZ and SZ: formal analysis. ZW: funding acquisition. QZ: investigation. QZ, YL, JZ, SZ, and ZW: writing-review and editing. All authors have read and approved the manuscript.

This work was supported by Shenzhen Fund for Guangdong Provincial High level Clinical Key Specialties (no. SZGSP012).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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