Behçet's spectrum disorders (BSD) describe a conceptual framework encompassing inflammatory conditions with overlapping clinical and genetic features with Behçet's disease. First introduced in 2020, the BSD concept was proposed to contextualize BD-like inflammation in pediatric and early-onset cases by linking clinical phenotypes to shared immune pathways and supporting earlier prioritization of genetic evaluation. A literature search was conducted in the PubMed and CNKI database using the following keywords: "Behçet's spectrum disorders", "Behçet's disease", "BD-like disease". We found several pediatric inflammatory disorders with Behçet-like mucocutaneous, gastrointestinal, or vasculitis symptoms that overlap with Behçet disease in key immunopathogenic pathways. Based on these findings, Behçet's spectrum disorders (BSD) are conceptualized as a mechanism-oriented framework encompassing a group of immune-mediated inflammatory conditions characterized by partial overlap with Behçet disease in clinical manifestations and immunopathogenic mechanisms. Within this spectrum, disorders cluster into two tiers: core BSD comprising monogenic diseases with recurrent mucosal ulceration and direct convergence on BD-defining pathways (including haploinsufficiency of A20, RELA, or NFKB1 haploinsufficiency, and ELF4 deficiency); peripheral BSD encompassing conditions with partial clinical overlap or indirect mechanistic proximity, such as polygenic disorders (recurrent aphthous stomatitis and PFAPA), BD-like vasculitic conditions such as DADA2 (deficiency of adenosine deaminase 2), and chromosomal abnormalities exemplified by trisomy 8. Although they are often misdiagnosed as Behçet disease, these conditions are biologically separate disorders that nonetheless share similar mucosal immune dysregulation. The BSD framework may help to facilitate earlier recognition and precise diagnosis of BD-related disorders in children, particularly those with atypical or syndromic presentations. The BSD framework integrates these insights to support earlier genetic screening and mechanism-guided management. However, this framework is not intended to replace current diagnostic criteria, but rather to support earlier recognition of BD-like phenotypes in children.
We aimed to characterize the phenotypes and genotypes of Chinese adult patients with systemic autoinflammatory diseases (SAIDs). We prospectively evaluated clinical and genetic features of 92 adult patients (≥16 years) suspected of SAIDs in the period from April 2015 to October 2017, at the adult SAIDs center, Peking Union Medical College Hospital. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. Clinical manifestations of these patients were compared with those from the pediatric populations and patients from other countries. A final diagnosis of SAIDs was reached in 50 patients, including 13 familial Mediterranean fever (FMF), 10 NLRP12-associated autoinflammtory disease (NLRP12-AID), 7 NLRP3-associated autoinflammatory disease (NLRP3-AID), 5 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), 3 Blau syndrome, 3 Yao syndrome (YAOS) and 9 periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). First disease onset during adulthood was observed in 30 patients, and the final diagnosis was delayed with a median time of 9 years. Adult monogenic SAIDs patients usually carried low-penetrance mutations and all gene variants were presented as heterozygosis or compound heterozygosis. Frequencies of clinical manifestations in Chinese adult SAIDs patients were similar with adult patients in other countries, but different from pediatric populations. FMF, NLRP3-AID, and NLRP12-AID are relatively common monogenic SAIDs in Chinese adults. Adult-onset SAIDs may be related to the presence of low-penetrance mutations, characterized by nonspecific, incomplete or atypical disease patterns compared with child-onset SAIDs, leading to a delay of diagnosis.
Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a multifactorial autoinflammatory disease (AID), which mainly affects children. There have been hardly any cases reported concerning the Chinese population. We aimed to describe the first cohort of adult PFAPA patients in China. We evaluated all the adult patients suffering from PFAPA syndrome diagnosed in our centre from April 2015 through March 2018. The patients were diagnosed clinically, and whole exome sequencing was performed in each patient to rule out mono-genic AIDs. During the study period, a total of 9 adult patients (8 men, 1 woman) with PFAPA syndrome were diagnosed. They all had disease onset in adulthood, and the mean age at onset was 25.2±9.5 years. The mean duration of attacks was 4.1±1.0 days, and the mean interval between attacks was 6.2±2.7 weeks. Apart from periodic fever, which was present in all patients, pharyngitis, cervical adenitis and aphthous stomatitis were present in 89%, 67% and 44% patients, respectively. Other common symptoms included fatigue (100%), headache (56%), and myalgia (55%). Inflammatory markers, except ferritin, increased during attacks and returned to normal afterwards. Glucocorticoids given at onset of attacks were effective, while colchicine and tonsillectomy were of no effect. Our study is the first to suggest the presence of PFAPA syndrome in the Chinese adult population. Clinicians should take into account PFAPA syndrome when diagnosing patients suffering from recurrent fevers of unknown origin, especially those with pharyngitis, cervical adenopathy and aphthous stomatitis.
