Systemic Manifestations of Behcet’s Disease in Children
Behçet’s Disease: Differences Between Pediatric and Adult Presentations—What the Uveitis Specialist
When Family History Speaks Loudly
A positive family history of Behçet's disease is significantly more frequent in pediatric-onset disease compared to adult-onset disease, suggesting a stronger genetic determinism in younger patients. In one pediatric tertiary centre cohort, familial cases accounted for up to 45% of the pediatric series. This pattern has been consistently reported across multiple comparative studies. 1, 2
The Incomplete Puzzle of Pediatric Behçet’s
Presentation with Incomplete Clinical Phenotype: Pediatric Behçet's disease frequently presents with an incomplete clinical phenotype, particularly in the early disease course. The latency between symptom onset and definitive diagnosis is consistently longer in children than in adults, and misclassification as recurrent aphthous stomatitis, PFAPA syndrome, or inflammatory bowel disease is common. This diagnostic challenge is specific to the pediatric age group. 3,4
Absence of Genital Ulcers Does Not Exclude Diagnosis
Genital ulcers are significantly less frequent in children compared to adults and may appear later in the disease course in pediatric patients. This difference is particularly marked in prepubertal children. Its absence should not preclude the diagnosis of Behçet's disease in a child with other characteristic features. 1,2
Lower Uveitis Burden in Pediatric Cohorts
The overall frequency of ocular involvement in pediatric Behçet's disease is lower than in adults, particularly in East and South Asian populations. Low prevalence of uveitis in juvenile-onset disease relative to adult-onset disease has been reported specifically in these geographic cohorts, contrasting with the high uveitis prevalence seen in adult Middle Eastern populations. 5
Gut Dominance in Pediatric Disease Expression
Gastrointestinal symptoms, including non-specific abdominal pain, nausea, and diarrhoea, are more prominent and more frequently reported in children compared to adults. A distinct gastrointestinal phenotypic cluster has been identified within pediatric Behçet's disease. Intestinal Behçet's mimicking Crohn's disease is particularly recognised in East Asian pediatric cohorts. 1,6
No Clear Male Predominance in Early-Onset Disease
In adult Behçet's disease, a male predominance is well-established in Middle Eastern and East Asian cohorts, with male sex associated with more severe ocular and vascular disease. In pediatric cohorts, the sex ratio is more equal, with some series reporting a slight female predominance at younger ages and a shift towards male predominance approaching adolescence. Within the pediatric group, males have higher rates of neurovascular disease while females have higher rates of genital ulceration. 2,7
Skin Clues in Pediatric Behçet’s
Folliculitis has been reported at a higher frequency in pediatric patients compared to adults in comparative cohort analyses, representing a relatively more prominent mucocutaneous feature of the pediatric disease phenotype compared to the adult pattern. 2
Pediatric Behçet’s: Less Severe, Yet Unpredictable
Pediatric Behçet's disease generally follows a milder overall course compared to adult disease, with lower rates of the most severe manifestations — ocular panuveitis, major vascular events, and parenchymal neuro-Behçet's. However, this is not universal, and a subset of children — particularly males with early-onset posterior uveitis or CNS involvement — experience significant morbidity comparable to adult disease. The generally milder course in children may in part reflect underdiagnosis due to the incomplete early phenotype rather than a true biological difference in disease severity. 1, 8, 9
Ocular Red Flags
- Recurrent non-granulomatous anterior uveitis — especially bilateral, acute onset, with hypopyon; a mobile shifting hypopyon is particularly characteristic of Behçet's disease
- Hypopyon uveitis in a child from any cause is uncommon — Behçet's disease should be in the differential alongside HLA-B27-associated disease
- Posterior uveitis or panuveitis with retinal vasculitis — particularly occlusive vasculitis affecting arteries and veins, with retinal ischaemia, neovascularisation, or vitreous haemorrhage
- Bilateral retinal vasculitis with a predilection for the posterior pole in a child or adolescent
- Vitritis with a recurrent, acute course — bilateral or with fellow eye episodes — without an identifiable infectious aetiology
- Optic disc oedema in the context of unexplained intraocular inflammation
- Recurrent uveitis of any type poorly responsive to standard topical therapy, recurring despite treatment, or associated with rapid visual decline
Systemic Red Flags
- Recurrent oral aphthous ulcers — three or more episodes per year, deeper and more painful than common aphthae, healing with scarring, appearing in crops
- Any episode of genital ulceration in a child or adolescent — highly specific, uncommon from other causes in this age group
- Recurrent unexplained fever without an identifiable infectious or autoimmune cause, particularly when cyclical or temporally associated with oral ulcers
- Skin lesions disproportionate to age — folliculitis, pseudofolliculitis, acneiform eruptions in a prepubertal or early pubertal child, or erythema nodosum on the lower limbs
- Positive pathergy response — sterile papule or pustule at skin prick site at 48 hours (supportive in endemic populations)
- Non-erosive, oligoarticular, intermittent arthritis or arthralgia involving large joints (knee, ankle) that does not fulfil criteria for juvenile idiopathic arthritis, especially with mucocutaneous features
- Recurrent abdominal pain, diarrhoea, or nausea in a child with recurrent oral ulceration — intestinal Behçet's disease closely mimics Crohn's disease
- Ileocaecal ulceration on imaging or endoscopy without a confirmed inflammatory bowel disease diagnosis
- Unexplained neurological symptoms — headache, behavioural change, focal deficits, or raised intracranial pressure — in a child with any mucocutaneous feature of Behçet's disease
- Cerebral venous sinus thrombosis or deep vein thrombosis in childhood without a coagulopathy, particularly in a child of Silk Road ancestry
References:
- Krause I, Uziel Y, Guedj D, et al. Childhood Behçet's disease: clinical features and comparison with adult-onset disease. Rheumatology (Oxford). 1999 May;38(5):457-62.
- Mastrolia MV, Bettiol A, Marrani E, et al. Behçet syndrome in children and adults: discovering similarities and differences by a comparative study. Rheumatology (Oxford). 2023 Feb 23;62(SI2):SI189-SI195.
- Yıldız M, Köker O, Adrovic A, et al. Pediatric Behçet's disease - clinical aspects and current concepts. Eur J Rheumatol. 2020 Feb;7(Suppl1):S38-S47.
- Costagliola G, Cappelli S, Consolini R. Behçet's Disease in Children: Diagnostic and Management Challenges. Ther Clin Risk Manag. 2020 Jun 11;16:495-507.
- Kitaichi N, Miyazaki A, Stanford MR et al. Low prevalence of juvenile-onset Behcet's disease with uveitis in East/South Asian people. Br J Ophthalmol. 2009 Nov;93(11):1428-30. doi: 10.1136/bjo.2008.
- Hu D, She CH, Bao HF, et al. Clinical heterogeneity and five phenotypes identified in pediatric Behçet's syndrome: a cohort study from Shanghai Behçet's syndrome database. World J Pediatr. 2024 Aug;20(8):801-808. doi: 10.1007/s12519-023-00785-9.
- Açarı C, İşgüder R, Torun R et al . Pediatric Behçet's disease: Experience of a single tertiary center. Arch Rheumatol. 2022 Oct 21;38(2):282-290.
- Giani T, Luppino AF, Ferrara G. Treatment Options in Pediatric Behçet's Disease. Paediatr Drugs. 2023 Mar;25(2):165-191.
- Ozen S, Eroglu FK. Pediatric-onset Behçet disease. Curr Opin Rheumatol. 2013 Sep;25(5):636-42. doi: 10.1097/BOR.0b013e328363ea8b.
