Behçet Disease in Children and Adolescents
Introduction to Behçet Disease in Children and Adolescents
Behçet Disease (BD) is a rare, chronic, multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. While it can affect individuals of all ages, pediatric-onset BD presents unique challenges in diagnosis and management. This condition is part of the spectrum of autoinflammatory diseases and can significantly impact the quality of life of affected children and adolescents.
The disease is named after the Turkish dermatologist Hulusi Behçet, who first described the triad of recurrent oral aphthous ulcers, genital ulcers, and uveitis in 1937. In pediatric patients, the disease often presents with incomplete manifestations, making early diagnosis challenging.
Epidemiology of Pediatric Behçet Disease
Behçet Disease is relatively rare in children, with the following epidemiological characteristics:
- Prevalence: Varies geographically, with higher rates along the ancient Silk Road (0.1-420 per 100,000 population)
- Age of onset: Usually between 20-40 years, but can occur in childhood (pediatric-onset BD accounts for 4-26% of all cases)
- Gender distribution: In adults, males are more commonly affected in Middle Eastern countries, while females predominate in Japan and Korea. In pediatric populations, the gender distribution is more balanced
- Geographical distribution: Highest prevalence in Turkey, Iran, and Japan; less common in Western countries
Pediatric-onset BD is associated with a more severe disease course and a higher prevalence of certain manifestations, such as gastrointestinal involvement, compared to adult-onset disease.
Etiology and Pathogenesis
The exact cause of Behçet Disease remains unknown, but it is believed to result from a complex interplay of genetic and environmental factors:
Genetic Factors:
- HLA-B51 allele: Strong association, increases risk by 5-10 times
- Other genes: IL10, IL23R-IL12RB2, STAT4, GIMAP, and UBAC2 have been implicated
Environmental Triggers:
- Infectious agents: Streptococcus sanguinis, Herpes simplex virus
- Stress
- Dietary factors
Immunological Mechanisms:
BD involves dysregulation of both innate and adaptive immune responses, characterized by:
- Hyperactive neutrophils
- Increased Th1 and Th17 responses
- Decreased regulatory T cell function
- Elevated levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
Clinical Manifestations in Pediatric Behçet Disease
The clinical presentation of BD in children and adolescents can be diverse and may evolve over time. Key manifestations include:
1. Mucocutaneous Lesions:
- Oral aphthous ulcers (most common and often the first symptom)
- Genital ulcers
- Skin lesions: erythema nodosum, papulopustular lesions, acneiform nodules
- Pathergy reaction (hypersensitivity of skin to minor trauma)
2. Ocular Involvement:
- Uveitis (anterior, posterior, or panuveitis)
- Retinal vasculitis
- Optic neuritis
3. Vascular Manifestations:
- Venous thrombosis
- Arterial aneurysms or occlusions
4. Neurological Involvement:
- Headache
- Aseptic meningitis
- Cerebral venous thrombosis
- Parenchymal lesions
5. Gastrointestinal Manifestations:
- Abdominal pain
- Diarrhea
- Gastrointestinal ulcers (often in the ileocecal region)
6. Musculoskeletal Symptoms:
- Arthralgia or arthritis (typically non-erosive)
- Myalgia
It's important to note that pediatric BD often presents with incomplete manifestations, and the full spectrum of symptoms may develop over years.
Diagnosis of Behçet Disease in Children and Adolescents
Diagnosing BD in pediatric patients can be challenging due to the variability of symptoms and the lack of a definitive diagnostic test. Several classification criteria have been proposed, but they are primarily validated for adult populations.
Diagnostic Approach:
- Clinical evaluation: Comprehensive history and physical examination
- Laboratory tests:
- Complete blood count
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
- HLA-B51 typing (supportive but not diagnostic)
- Pathergy test: Intradermal injection of sterile saline (positive if papule or pustule forms within 48 hours)
- Imaging studies:
- Ocular: Fluorescein angiography, optical coherence tomography
- Neurological: MRI brain and spine
- Vascular: Doppler ultrasonography, CT angiography, or MR angiography
- Tissue biopsy: May be necessary to exclude other conditions
Classification Criteria:
While no specific criteria are universally accepted for pediatric BD, the following are often used:
- International Study Group (ISG) criteria (1990)
- International Criteria for Behçet's Disease (ICBD) (2006, revised 2014)
- Pediatric Behçet's Disease (PEDBD) criteria (2015)
The PEDBD criteria are more sensitive for pediatric populations and include:
- Recurrent oral aphthosis (at least 3 attacks/year)
- Genital ulceration
- Ocular involvement
- Skin involvement
- Neurological signs
- Vascular signs
A diagnosis of pediatric BD is considered in patients with at least three of these six criteria.
Treatment of Behçet Disease in Children and Adolescents
Management of pediatric BD is multidisciplinary and aims to control inflammation, prevent organ damage, and improve quality of life. Treatment is tailored to the severity and organ involvement.
General Principles:
- Early intervention
- Regular monitoring and follow-up
- Patient and family education
Pharmacological Treatment:
- Topical Therapies:
- Corticosteroids for oral and genital ulcers
- Sucralfate suspension for oral ulcers
- Systemic Medications:
- Colchicine: For mucocutaneous and joint manifestations
- Corticosteroids: For acute flares and severe organ involvement
- Immunosuppressants:
- Azathioprine
- Cyclosporine A (especially for ocular involvement)
- Mycophenolate mofetil
- Methotrexate
- Biologics:
- TNF-α inhibitors (infliximab, adalimumab, etanercept)
- Interferon-α
- IL-1 inhibitors (anakinra, canakinumab)
- Anticoagulation: For vascular involvement
Non-Pharmacological Approaches:
- Dietary modifications (avoiding triggering foods)
- Stress management techniques
- Physical therapy for joint involvement
- Psychological support
Management of Specific Manifestations:
- Ocular: Collaboration with ophthalmologists, aggressive immunosuppression
- Neurological: High-dose corticosteroids, immunosuppressants, anti-TNF therapy
- Vascular: Anticoagulation, immunosuppression, possible surgical intervention
- Gastrointestinal: Sulfasalazine, corticosteroids, immunosuppressants
Treatment decisions should be made in conjunction with pediatric rheumatologists and other relevant specialists, considering the patient's age, disease severity, and potential side effects of medications.
Prognosis and Long-term Outcomes
The prognosis of Behçet Disease in children and adolescents is variable and depends on several factors:
Factors Influencing Prognosis:
- Age of onset
- Gender (males often have more severe disease)
- Pattern and severity of organ involvement
- Early diagnosis and treatment
- Adherence to therapy
Long-term Outcomes:
- Ocular involvement: Major cause of morbidity; can lead to vision loss if not adequately treated
- Neurological involvement: Associated with significant disability and mortality
- Vascular involvement: Can lead to life-threatening complications
- Mucocutaneous manifestations: Generally good prognosis but can significantly impact quality of life
Disease Course:
BD typically follows a relapsing-remitting course. With appropriate treatment, many patients achieve remission or low disease activity. However, lifelong monitoring is often necessary.
Transition to Adult Care:
As pediatric patients with BD transition to adulthood, a coordinated approach between pediatric and adult rheumatologists is crucial to ensure continuity of care.
Quality of Life:
BD can significantly impact physical, psychological, and social aspects of life. Comprehensive care addressing all these domains is essential for optimal long-term outcomes.
Behçet Disease in Children and Adolescents
- What is Behçet Disease?
A multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, and ocular inflammation - What is the typical age of onset for pediatric Behçet Disease?
Usually in late childhood or adolescence, but can occur earlier - What is the most common initial symptom of Behçet Disease in children?
Recurrent oral aphthous ulcers - How often do oral ulcers typically recur in Behçet Disease?
At least three times in a 12-month period - What is the characteristic eye involvement in Behçet Disease?
Uveitis, often bilateral and recurrent - What is the pathergy test, and how is it relevant to Behçet Disease?
A skin prick test that shows hypersensitivity to minor trauma, often positive in Behçet Disease - What is the triad of symptoms classically associated with Behçet Disease?
Oral ulcers, genital ulcers, and uveitis - Which genetic marker is associated with an increased risk of Behçet Disease?
HLA-B51 - What is the geographic distribution of Behçet Disease?
More common along the ancient Silk Road, from the Mediterranean to East Asia - What is the male to female ratio in pediatric Behçet Disease?
Approximately equal, unlike adult Behçet Disease which has a male predominance - What type of vasculitis is associated with Behçet Disease?
Variable vessel vasculitis, affecting arteries and veins of all sizes - What neurological manifestations can occur in pediatric Behçet Disease?
Headaches, aseptic meningitis, and rarely, cerebral venous thrombosis - What gastrointestinal symptoms are common in pediatric Behçet Disease?
Abdominal pain, diarrhea, and gastrointestinal ulcers - What is the most common joint involvement in pediatric Behçet Disease?
Oligoarthritis, typically affecting knees and ankles - What skin manifestations, other than pathergy, are seen in Behçet Disease?
Erythema nodosum, papulopustular lesions, and acneiform nodules - What is the primary goal of treatment in pediatric Behçet Disease?
To control inflammation, prevent organ damage, and improve quality of life - What medications are commonly used to treat mucocutaneous symptoms in Behçet Disease?
Topical corticosteroids, colchicine, and systemic corticosteroids - What is the role of immunosuppressive agents in treating Behçet Disease?
Used for severe organ involvement or refractory disease - Which immunosuppressive drug is often used as first-line therapy for severe Behçet Disease?
Azathioprine - What is the role of anti-TNF agents in treating Behçet Disease?
Used for refractory cases, particularly those with severe ocular or neurological involvement - How does the clinical course of Behçet Disease differ in children compared to adults?
Generally milder in children, with less frequent major organ involvement - What is the significance of family history in pediatric Behçet Disease?
A positive family history is more common in pediatric-onset cases - What cardiac manifestations can occur in Behçet Disease?
Pericarditis, myocarditis, and rarely, intracardiac thrombus - What is the role of corticosteroids in treating ocular Behçet Disease?
Used for acute flares, often in combination with immunosuppressive agents - What is the prognosis for children with Behçet Disease?
Generally good with proper treatment, but the disease can be chronic and relapsing - How does Behçet Disease affect growth and development in children?
It may cause growth retardation and delayed puberty in some cases - What is the recommended frequency of ophthalmological examinations in pediatric Behçet Disease?
Every 3-6 months, or more frequently if there is active eye involvement - What is the role of anticoagulation in Behçet Disease?
Used in cases with vascular involvement, particularly venous thrombosis - How does pregnancy affect the course of Behçet Disease in adolescent females?
It may exacerbate symptoms, particularly mucocutaneous lesions - What is the importance of psychological support in managing pediatric Behçet Disease?
To address the impact of chronic illness on mental health and quality of life
