Von Hippel-Lindau syndrome

Disease Description (Causes and Symptoms)

• Definition: Behçet's disease is a chronic inflammatory disease in which inflammation repeatedly occurs in blood vessels throughout the body (arteries and veins), presenting with recurrent oral and genital ulcers, uveitis (eye inflammation), skin lesions, joint symptoms, and vascular, neurological, and gastrointestinal involvement.
• Causes/pathophysiology: The exact cause is unknown. It is presumed that genetic predisposition (association with HLA‑B51) and environmental factors (an excessive immune response to potential infectious agents) combine to cause vasculitis through abnormal activity of immune cells. Inflammation-induced vascular endothelial damage may lead to venous thrombosis, arterial lesions, and intestinal, brain, and eye complications.
• Main symptoms (frequency and characteristics):
  • Recurrent, severely painful oral ulcers (in nearly all patients)
  • Recurrent genital ulcers (men: penis/scrotum; women: vulva, etc.)
  • Eye symptoms: anterior and posterior uveitis, eye pain, redness, and decreased vision (risk of blindness)
  • Skin lesions: acne-like lesions, erythema nodosum, vasculitic papules, etc.
  • Joints: transient arthritis (knees, ankles, etc.); joint deformities are uncommon
  • Blood vessels: mainly venous thrombosis; severe cases may involve large-vein occlusion or aneurysms
  • Nervous system: aseptic meningitis, parenchymal brain lesions, and possible thrombotic stroke
  • Digestive system: colon and stomach ulcers; perforation is rare

Treatment Methods

• Treatment goals: Control acute inflammation and prevent long-term damage (particularly damage to vision, the brain, and major blood vessels). Because the disease has a relapsing course, long-term follow-up and medication adjustment are necessary.
• Topical treatment: For oral and genital ulcers, topical steroid ointment (or oral steroid gel), antimicrobial mouthwash, and topical analgesics.
• First-line drug therapy (depending on symptoms and severity):
  • Colchicine: Effective for mucosal and skin lesions and arthropathy.
  • Systemic steroids (such as prednisone): Used to control acute, severe, widespread inflammation (involving the eyes, blood vessels, nervous system, or intestinal mucosa); a short course of high-dose treatment is followed by gradual tapering.
  • Immunosuppressants: Azathioprine (to prevent eye and systemic symptoms), cyclosporine (effective for severe eye disease, but requires caution in patients with neurological involvement), cyclophosphamide (for severe vascular or visceral involvement), etc.
  • Biologics: Anti-TNF agents (infliximab and adalimumab) are effective for refractory eye, vascular, intestinal, and neurological lesions. Interferon-α is also used in some patients.
  • Other treatments: Thalidomide (potent but teratogenic and contraindicated in people of childbearing potential), and apremilast (a PDE4 inhibitor), which has been approved and used in some cases as a topical and oral option for oral ulcers.
• Thrombosis treatment: Because inflammatory vascular damage is the main mechanism of Behçet-related venous thrombosis, immunosuppressive treatment takes priority. Anticoagulant therapy is discussed on a case-by-case basis and may be administered concurrently under specialist judgment when there is a risk of occlusion or embolism, or when coronary or pulmonary thrombosis is present (controversial).
• Procedures/surgery: Vascular surgery or general surgical intervention may be necessary for complications such as aneurysms, intestinal perforation, or major-vessel occlusion.
• Lifestyle management/follow-up: Regular ophthalmologic examinations (prevention and early treatment of uveitis), infection prevention (consider vaccination and evaluation before immunosuppression), and monitoring for medication side effects during long-term treatment (such as osteoporosis, infection, and liver or kidney dysfunction).

Checklist Before an Outpatient Visit (Including Example Questions)

• Items and records to prepare:
  • List of current medications (including prescriptions, over-the-counter medicines, herbal medicines, and supplements)
  • Previous test records (ophthalmology reports, MRI/CT scans, blood tests, thrombosis-related tests, etc.)
  • Recent symptom diary (frequency and duration of oral and genital ulcers, changes in vision, photographs taken when skin lesions occur, etc.)
  • History of previous hospitalization, surgery, severe thrombosis, or brain- or eye-related conditions
  • Inform the doctor about the possibility of pregnancy or plans for pregnancy
• Important information to tell the doctor first during the outpatient visit:
  • Recent changes in vision (blurred vision, eye pain, halos around lights, etc.) — high urgency
  • Severe swelling or pain in the lower extremities (suspected deep-vein thrombosis/embolism)
  • Symptoms of complications such as high fever, severe abdominal pain, chest pain, or difficulty breathing
• Example questions (items patients can ask on their own during the visit):
  • "How do the frequency and severity of my recent ulcer outbreaks compare with the treatment goals?"
  • "How often do I need an ophthalmologic evaluation?"

Examples of General Questions to Ask the Doctor

• "What are the main side effects of this medication, and which tests should be monitored?"
• "Are there any interactions with other medications (or supplements) I am taking?"
• "Which medications should I stop or replace during pregnancy or breastfeeding?"
• "What is your expectation for the prognosis (vision preservation and likelihood of recurrence)?"
• "When can I receive vaccinations, especially live vaccines?"

Examples of Disease-Specific Questions

• "For my (or the patient's) ophthalmologic findings (for example, recurrent anterior and posterior uveitis), when would you recommend starting immunosuppressive treatment or anti-TNF treatment? How can the risk of blindness be reduced?"
• "A venous thrombosis in the lower extremity has recently been suspected. In this case, should anticoagulant therapy be started immediately, or should immunosuppressive treatment be given first?"

Additional Summary (Clinical Points)

• Diagnosis is primarily based on clinical findings (recurrent oral and genital ulcers and systemic symptoms) and supplementary tests (pathergy test, HLA‑B51, imaging studies, etc.). No single test can definitively confirm the diagnosis.
• Early specialist intervention and aggressive immunosuppressive treatment are important for improving the prognosis when there is serious organ involvement (the eyes, brain, or major blood vessels).
• Long-term follow-up and monitoring for medication side effects (blood tests, liver and kidney function, ophthalmologic examinations, etc.) are essential.