Behcet Disease: Symptoms, Types, Causes and Treatment

Behcet disease is a rare, chronic inflammatory condition that can affect multiple organ systems. Known for its unpredictable flare-ups and remissions, Behcet disease presents unique challenges for diagnosis and treatment. Understanding its symptoms, types, causes, and management approaches is crucial for patients, caregivers, and healthcare professionals alike. This article offers a comprehensive, evidence-based overview, synthesizing the latest research to clarify what makes Behcet disease both complex and fascinating.

Symptoms of Behcet Disease

Behcet disease is notorious for its wide range of symptoms, which can affect nearly every organ in the body. Early recognition and understanding of these manifestations are vital for timely diagnosis and effective management.

Symptom	System/Location	Frequency/Notes	Source(s)
Oral ulcers	Mouth	Nearly universal (>95–100%)	2 5 6 7 8
Genital ulcers	Genital mucosa	Common (60–90%)	2 5 6 7 8
Skin lesions	Skin	Erythema nodosum, pseudofolliculitis (40–90%)	2 5 6 7
Eye involvement	Ocular (uveitis)	45–90%, can cause vision loss	2 5 6 7 8
Joint symptoms	Joints	Arthritis, arthralgia (30–90%)	6 7
Neurological	CNS	Headache, ataxia, hemiplegia (2–38%)	1 5 6 7 8
Gastrointestinal	GI tract	Abdominal pain, diarrhea, ulcers (4–38%)	4 6 7 8
Vascular	Vessels	Thrombosis, aneurysms (2–50%)	6 7 18
Pulmonary	Lungs	Rare; chest pain, cough	3 6 7
Pathergy test	Skin	Positive in 8–70% (diagnostic clue)	2 3 6 7

Table 1: Key Symptoms

Common Clinical Features

The “classic triad” of Behcet disease includes recurrent oral aphthous ulcers, genital ulcers, and eye inflammation (often uveitis) 2 3 5 6 7 8. Almost all patients experience painful mouth ulcers, which can be mistaken for common canker sores but are more frequent and severe.

Skin and Mucosal Manifestations

• Oral ulcers: The hallmark sign, nearly always present, recurring multiple times per year.
• Genital ulcers: Painful, may scar, and are often less frequent than oral ulcers.
• Skin lesions: Erythema nodosum (red, tender nodules), pseudofolliculitis (acne-like spots), and papulopustular lesions are typical 2 6 7.

Eye Involvement

• Uveitis: Inflammation of the uveal tract in the eye can cause pain, redness, blurred vision, and, if untreated, permanent vision loss 2 5 6 7 8.
• Retinal vasculitis: Can lead to severe visual impairment, especially prevalent in males 5.

Neurological and Systemic Symptoms

• Neurological: Headaches, gait disturbances, sensory deficits, weakness, and in severe cases, symptoms mimicking multiple sclerosis (neuro-Behcet) 1 5 6 7 8.
• Gastrointestinal: Abdominal pain, diarrhea (sometimes bloody), and ulcerations, especially in the ileocecal region 4 6 7 8.
• Vascular: Thrombosis (e.g., deep vein thrombosis), arterial inflammation, and aneurysms, which can be life-threatening 6 7 18.
• Others: Joint pain, arthritis, pulmonary symptoms (rare), and positive pathergy test (development of a papule after skin prick) 2 3 6 7.

Disease Course and Variability

Symptoms tend to flare and remit unpredictably. The range and severity of symptoms can vary significantly between individuals and even within the same patient over time 8 13.

Types of Behcet Disease

Behcet disease is not a one-size-fits-all condition. Its presentation can be classified into different types based on the systems affected, which helps guide management and prognosis.

Type	Main Features	Special Notes	Source(s)
Mucocutaneous	Oral/genital ulcers, skin lesions	Most common, initial presentation	2 6 7 8 13
Ocular Behcet	Uveitis, retinal vasculitis	Risk of vision loss	2 5 6 7 8
Neuro-Behcet	CNS involvement (headache, ataxia, paralysis)	Severe, can mimic MS, poor prognosis	1 6 7 8
Vascular Behcet	Thrombosis, aneurysms, vascular occlusion	High morbidity, mortality risk	6 7 18
Gastrointestinal	GI ulcers, bleeding, perforation	Ileocolic region often affected	4 6 7 8
Pulmonary/cardio	Pulmonary artery involvement, cardiac signs	Very rare; significant complications	3 6 7

Table 2: Behcet Disease Types

Mucocutaneous Type

The most frequent presentation involves mucous membrane and skin findings—recurrent oral and genital ulcers, and skin lesions. For many patients, these are the only symptoms experienced 2 6 7 8 13.

Ocular Behcet

Eye involvement, especially uveitis and retinal vasculitis, is a major cause of disability due to risk of vision loss. Males are more likely to suffer severe ophthalmic complications 5 6 7 8.

Neuro-Behcet

When Behcet disease affects the nervous system (neuro-Behcet), symptoms can include:

• Severe headaches
• Unsteadiness, gait abnormalities
• Sensory disturbances (paresthesia)
• Weakness, hemiplegia, ataxia
• Diplopia (double vision)

Neuro-Behcet can mimic other neurological diseases such as multiple sclerosis and often requires intensive management 1 6 7 8.

Vascular Behcet

Vascular involvement may include superficial and deep vein thrombosis, arterial aneurysms (especially pulmonary arteries), and occlusive vasculopathy. These complications are associated with increased risk of morbidity and early mortality 6 7 18.

Gastrointestinal and Other Types

Gastrointestinal Behcet primarily affects the ileocecal region, causing recurrent abdominal pain, ulcers, bleeding, and, rarely, perforation 4 6 7 8. Pulmonary and cardiac involvement is uncommon but potentially life-threatening, manifesting as pulmonary artery aneurysms, hemorrhage, or cardiac dysfunction 3 6 7.

Causes of Behcet Disease

The exact cause of Behcet disease remains elusive, but advances in research have illuminated key factors contributing to its development.

Factor	Description	Significance	Source(s)
Genetics	HLA-B51, other gene variants	Increases susceptibility	2 10 11 12 13
Immune response	Aberrant Th1/Th17, neutrophil hyperactivity	Drives inflammation	9 10 11 12 14
Infectious	Streptococcus, HSV, altered microbiome	Triggers in susceptible hosts	2 10 11 12 14
Environment	Geography (Silk Road), climate, unknown factors	Influences prevalence, symptoms	2 5 6 7 11 14

Table 3: Behcet Disease Causes and Risk Factors

Genetic Susceptibility

• HLA-B51: The strongest known genetic risk factor—presence increases the risk but is not determinative. Other genes related to immune regulation (e.g., cytokine genes, ERAP1) are also implicated 2 10 11 12 13.
• Non-HLA genes: Variants affecting cytokines and immune pathways contribute to disease risk 11 12.

Immune Dysregulation

• Innate and adaptive immunity: Overactivity leads to excessive inflammation, especially Th1 and Th17 T cells, and increased neutrophil action 9 10 11 12.
• Cytokines: Elevated pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-17) are found in patients and drive tissue damage 9 10 11 12.

Infectious and Environmental Triggers

• Microbial agents: Infections with Streptococcus sanguinis, herpes simplex virus (HSV), or changes in the oral/gut microbiome may trigger disease in genetically predisposed individuals 2 10 11 12 14.
• Environmental factors: Higher prevalence along the ancient Silk Road suggests a combination of genetic and environmental influences. Climatic factors may influence symptom patterns (e.g., nasal ulcers in Mongolia) 2 5 6 7 11 14.

Pathogenesis Overview

Behcet disease is best viewed as an autoinflammatory condition, where genetic predisposition sets the stage for abnormal immune responses to environmental or infectious triggers, culminating in multi-system inflammation 10 11 12 14.

Treatment of Behcet Disease

Managing Behcet disease is challenging and must be tailored to the patient’s specific symptoms and organ involvement. Recent advances in therapy offer hope for better long-term outcomes.

Treatment	Main Use/Symptoms	Notes/Effectiveness	Source(s)
Corticosteroids	Acute flares, vital organ disease	Mainstay for rapid inflammation control	2 15 16
Colchicine	Mucocutaneous, arthritis	Effective, esp. for erythema nodosum	2 16
Immunosuppressants	Severe organ involvement	Azathioprine, cyclosporine, methotrexate	2 15 16
Biologics	Refractory/severe cases	TNF-α inhibitors, IFN-α, IL-6 blockers	2 15 16 17 19
Topical therapies	Oral/genital ulcers	Local corticosteroids, anesthetics	16
NSAIDs	Arthritis, mild joint pain	Symptomatic relief	2 16
Surgical intervention	Vascular, GI emergencies	For aneurysms, perforation	15 16 18

Table 4: Key Behcet Disease Treatments

Conventional Therapies

• Corticosteroids: Used for rapid control of inflammation, especially in serious organ involvement (eye, CNS, vascular). Often combined with other agents for long-term control 2 15 16.
• Colchicine: Effective for mucocutaneous symptoms and arthritis, particularly in women 2 16.
• Immunosuppressants: Azathioprine, cyclosporine, methotrexate, and cyclophosphamide are used for severe or refractory disease, especially with eye, CNS, or vascular involvement 2 15 16.

Biologic and Targeted Therapies

• TNF-α inhibitors (e.g., infliximab): Highly effective in refractory cases, especially for vascular, ocular, and GI involvement 15 16 17 19.
• Interferon alpha: Used for resistant ocular and extraocular symptoms 2 12 16.
• IL-6 inhibitors (e.g., tocilizumab): Show promise in refractory neuro-, ocular-, and vascular-Behcet, but less so for mucocutaneous symptoms 19.
• Other agents: Thalidomide (mucocutaneous), JAK inhibitors (tofacitinib, for refractory cases), and others are under investigation 15 16 17.

Symptomatic and Supportive Treatments

• Topical therapies: Local corticosteroids, anesthetics for ulcer pain, and antiseptics help manage symptoms 16.
• NSAIDs: Provide relief from joint pain but are less effective for arthritis 2 16.

Special Considerations

• Surgical interventions: Reserved for life-threatening complications (e.g., vascular aneurysms, GI perforation) 15 16 18.
• Treatment individualization: Therapy is chosen based on organs involved, severity, patient age, and comorbidities 2 15 16.
• Monitoring: Regular follow-up is crucial due to relapsing-remitting nature and risk of irreversible damage, especially to eyes and CNS 2 13 15.

Conclusion

Behcet disease is a complex, multi-system inflammatory condition that requires a keen eye for diagnosis and a personalized approach to management. Its unpredictable course and diverse manifestations can be daunting, but advances in understanding and therapy are improving outcomes.

Key Points:

• Behcet disease presents with recurrent oral and genital ulcers, skin lesions, and can affect the eyes, nervous system, blood vessels, and other organs 2 5 6 7 8.
• There are several clinical types, with severity and prognosis depending on the organs involved 1 2 5 6 7 8 13 18.
• The disease arises from a combination of genetic susceptibility (especially HLA-B51) and immune dysregulation, often triggered by environmental or infectious factors 2 10 11 12 13.
• Treatment is tailored to symptom severity and organ involvement, combining corticosteroids, immunosuppressants, and increasingly, biologic therapies 2 15 16 17 19.
• Early recognition and multidisciplinary management are essential to reduce morbidity and prevent serious complications.

With ongoing research and new therapies, the outlook for patients with Behcet disease continues to improve, offering hope for better quality of life and disease control.