Challenging to Live With, Challenging to Diagnose
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Understanding
Behçet’s Disease Recognizing and
Diagnosing
Behçet’s Disease The Burden of
Behçet’s Disease
This learning module is intended for healthcare professionals in the United States only.
Understanding Behçet’s Disease
How many patients with Behçet’s Disease
do you currently manage in your clinic each year?
a
None
b
1-5
c
6-10
d
11-25
e
26-50
f
>50
SUBMIT
Behçet’s Disease Is a Chronic, Multisystem, Inflammatory Disorder
Most Commonly Found in Regions Along the “Silk Road”
  • Behçet’s Disease is found worldwide, with significant regional differences in incidence
  • The highest number of incidences is found in the Mediterranean, Middle East, and Far East, between the latitudes of 30° N and 45° N
  • Reports of Behçet’s Disease in other parts of the world including Russia, Mongolia, Latin America, New Zealand, and Australia total less than 200 patients
*Dot size reflects prevalence.

References: 1. Adapted with permission from Cho SB et al. Yonsei Med J. 2012;53(1):35-42. 2. Leonardo NM, McNeil J. Int J Rheumatol. 2015;2015:945262.

In the United States, the Prevalence of Behçet’s Disease
Is 5.2 Cases per 100,000 People
  • Turkey has the highest prevalence of Behçet’s Disease in the world, at 421 cases per 100,000 people, followed by Iran, Saudi Arabia, and Iraq
  • The lowest prevalence of Behçet’s Disease is found in the United Kingdom, Portugal, Germany, Sweden, and the United States
Leonardo NM, McNeil J. Int J Rheumatol. 2015;2015:945262.
Behçet’s Disease Is Linked to Genetic and Environmental
Factors That May Activate an Autoimmune Cascade1
(Click on the plus buttons to learn more.)
References: 1. Alpsoy E. J Dermatol. 2016;43(6):620-632. 2. Cho SB et al. Yonsei Med J. 2012;53(1):35-42. 3. Galeone M et al. Patholog Res Int. 2012;2012:595380. 4. Hatemi G et al. Clin Exp Rheumatol. 2017;35(suppl 108):S-3-S-15. 5. Na SY, Park M-J, Park S, Lee E-S. Clin Exp Rheumatol. 2013;31(suppl 77):S32-S40. 6. Chi W, et al. Invest Opthamol Vis Sci. 2008;49(7):3058-3064. 7. Lopalco G, et al. Front Immunol. 2017;8:10. 8. Nanke Y, Yago T, Kotake S. J Clin Med. 2017;6:8.
Multiple Systems Can Be Affected by Behçet’s Disease,
But Oral Ulcers Are the Most Commonly Observed Manifestation
(Click on the plus buttons to learn more.)
Manifestations of Behçet’s Disease With Approximate Prevalences
GI, gastrointestinal.

Barnes CG. History and diagnosis. In: Yazici Y, Yazici H, eds. Behçet’s Syndrome. Springer; 2010:7-33.

Multiple Systems Can Be Affected by Behçet’s Disease,
But Oral Ulcers Are the Most Commonly Observed Manifestation1,2

Individuals may experience a range of different recurring and remitting manifestations that may not occur at the same time.3,4

There is no universally recognized diagnostic test for Behçet’s Disease. The ISG Criteria (1990) can aid diagnosis when recurrent oral ulceration is observed with at least 2 additional manifestations (recurrent genital ulceration, eye lesions, skin lesions, or positive result on pathergy testing).5

ISG, International Study Group.

References: 1. Barnes CG. History and diagnosis. In: Yazici Y, Yazici H, eds. Behçet's Syndrome. Springer;2010:7-33. 2. Zeidan MJ et al. Autoimmun Highlights. 2016;7(1):12. 3. Cho SB, Cho S, Bang D. Yonsei Med J. 2012;53(1):35-42. 4. Ambrose NL, Haskard DO. Nat Rev Rheumatol. 2013;9(2):79-89. 5. International Study Group for Behçet's Disease. Lancet. 1990;335(8697):1078-1080.

Check Your Knowledge
Which of the following statements are true?
(Select all that apply.)
a
Genital ulcers are the most commonly observed clinical manifestation of Behçet’s Disease
b
Behçet’s Disease is linked to genetic and environmental factors that may activate an autoimmune cascade
c
Behçet’s Disease is most prevalent in the United Kingdom, Portugal, Germany, Sweden, and the United States
d
Oral ulcers are typically the earliest and most frequent manifestation of Behçet’s Disease
e
None of the above
SUBMIT
What clinical manifestations most commonly prompt a
referral to your office for suspected Behçet’s Disease?
(Select all that apply.)
a
Oral ulcers
b
Ocular involvement
c
Skin lesions
d
Vascular involvement
e
Neurologic involvement
f
Joint involvement
g
Genital ulcers
h
Gastrointestinal involvement
i
None of the above
SUBMIT
You have reached the end of the learning module section on
“Understanding Behçet’s Disease.”

Thank you for your time and attention.

Please fill out a brief survey below.
1
I am a:
Specialty:
2
Please rate your level of agreement with the following statement:
This section of the learning module improved or reaffirmed my understanding of the signs and symptoms of Behçet’s Disease.
(1=strongly disagree)
(5=strongly agree)
SUBMIT
Learn More About Behçet’s Disease

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This learning module is intended for healthcare professionals in the United States only.

Recognizing and Diagnosing Behçet’s Disease
Check Your Knowledge
What is the average time from symptom onset
to diagnosis of Behçet’s Disease?
a
≤1 year
b
2 years
c
3 years
d
4 years
e
5 years
f
6-10 years
g
>10 years
SUBMIT

The mean duration from onset of symptoms to diagnosis of Behçet’s Disease is 5.3 years.*

Diagnosis tends to take longer in patients having only mucocutaneous lesions (1.13 ± 2.4 years) than in patients having more serious organ involvement (0.88 ± 1.9 years).*,†

*Study of 661 patients at the Behçet’s Disease Units of Akdeniz, Cukurova, Firat, Gazi, Inonu, and Mersin Universities. †Mean ± SD.

SD, standard deviation.

Alpsoy E et al. Br J Dermatol. 2007;157(5):901-906.

Diagnosis of Behçet’s Disease Is Complex and
Relies on the Exclusion of Alternative Diagnoses1,2
(Click on the plus buttons to learn more)
GI, gastrointestinal; MAGIC, mouth and genital ulcers with inflamed cartilage; SAPHO, synovitis, acne, pustulosis, hyperostosis, osteitis.

References: 1. Yazici H et al. Nat Rev Rheumatol. 2018;14(2):107-119. 2. Ambrose NL, Haskard DO. Nat Rev Rheumatol. 2013;9(2):79-89.

Some Elements Strengthen a Diagnosis of Behçet’s Disease
(Click on the plus buttons to learn more.)

Strong Elements*
Oral ulcers
  • Absence strongly suggests another diagnosis
Ocular disease
  • A top discriminatory finding in a formal analysis in formulating disease criteria
  • A disease-defining factor in a factor analysis
  • Unique findings found by ophthalmologists masked to disease at other sites
Genital ulceration
  • A top discriminatory finding in a formal analysis in formulating disease criteria
Major vascular involvement
  • Pulmonary arterial aneurysms are almost unique to Behçet’s Disease
Parenchymal neurologic disease
  • As shown in a comparative and masked study, isolated brainstem atrophy and lesions extending from the brainstem to basal ganglia are quite suggestive of Behçet’s Disease
Weak Elements†
Geographic variation in disease expression
  • GI disease is more frequent in Far East Asia, but infrequent in Turkey
  • Vascular disease is less common in Far East Asia than in Turkey and other Middle Eastern countries
  • Milder disease has been reported among patients from non-endemic areas
Association with Crohn’s disease
  • Difficult to distinguish from Crohn’s disease if extraintestinal manifestations are not present
Distinct disease subsets
  • Vascular disease and acne-arthritis-enthesitis clusters are 2 important subsets
  • Presence of these subsets suggests more than 1 common pathogenetic mechanism
Different response to various drugs
  • Varying response to immunosuppressive treatments could be another indicator of more than 1 disease mechanism
*A strong element is defined as a feature that attempts to define Behçet’s Disease as a distinct nosologic entity with a unique pathogenesis and more or less unique disease features. †A weak element points to more than 1 common pathogenetic mechanism.

Yazici H et al. Nat Rev Rheumatol. 2018;14(2):107-119.

The ISG Criteria (1990) Can Aid in the Diagnosis of Behçet’s Disease
(Click on the plus buttons to learn more.)

Recurrent Oral Ulceration (aphthous or herpetiform) observed by the
physician or patient recurring at least 3 times in one 12-month period

Plus at least 2 of the following criteria:

There is no universally recognized diagnostic test for Behçet’s Disease and diagnosis is primarily based on clinical criteria.

ISG, International Study Group.

International Study Group for Behçet’s Disease. Lancet. 1990;335(8697):1078-1080.

A 31-Year-Old Female Visits Your Clinic…
Presentation
  • Genital ulcers, disabling pain, arthralgia of the knees, and erythema nodosum on the lower legs
Medical history and exam
  • History of genital ulcers with scarring 5 years before
  • Normal abdominal exam
  • Negative for herpes simplex virus, HIV, and other sexually transmitted infections
  • Assessment of hematology and clinical chemistry parameters revealed no abnormalities
  • Revealed a history of oral ulcers occurring 3-4 times per year over the past 5 years
This patient scenario is hypothetical in nature and provided for general medical education purposes.
Check Your Knowledge
Which aspects of this patient’s medical history and exam
most strongly indicate a diagnosis of Behçet’s Disease?
(Select all that apply.)
a
History of genital ulcers
b
Disabling pain
c
Arthralgia of the knees
d
Erythema nodosum on the lower legs
e
Normal abdominal exam
f
History of recurrent oral ulcers
g
Negative for sexually transmitted infections
SUBMIT

Recurrent oral ulcers and genital ulcers are both strong elements of Behçet’s Disease that are also included in the ISG Criteria.1,*

While erythema nodosum may not be considered a strong element of Behçet’s Disease, it is also included in the ISG Criteria and can aid in diagnosis. Similarly, joint involvement (such as arthralgia of the knees) is a common clinical manifestation observed in approximately 45% of patients with Behçet’s Disease. When considered together with negative results from STI testing, all of these elements can aid in diagnosis.1-3

*A strong element is defined as a feature that attempts to define Behçet’s Disease as a distinct nosologic entity with a unique pathogenesis and more or less unique disease features. STI, systolic time interval.

1. Yazici H et al. Nat Rev Rheumatol. 2018;14(2):107-119. 2. International Study Group for Behçet’s Disease. Lancet. 1990;335(8697):1078-1080. 3. Barnes CG. History and diagnosis. In: Yazici Y, Yazici H, eds. Behçet’s Syndrome. Springer; 2010:7-33.

Check Your Knowledge
Along with recurrent oral ulceration, which clinical manifestations are included
in the ISG Criteria as indicators of a potential Behçet’s Disease diagnosis?
(Drag and drop the correct answers into the fields below.)
Deep Venous Occlusions
Positive Results on Pathergy Testing
Read by the physician
at 24-48 hours
Recurrent Genital Ulceration
Aphthous ulceration or scarring observed
by the physician or patient
Parenchymal Disease
Arthritis
Eye Lesions
Anterior uveitis, posterior uveitis, or cells
in vitreous on slit-lamp examination

or

Retinal vasculitis observed by
an ophthalmologist
Skin Lesions
Erythema nodosum observed by the
physician or patient, pseudofolliculitis,
or papulopustular lesions

or

Acneiform nodules observed by the
physician in postadolescent patients
not on corticosteroid treatment
The ISG Criteria (1990)

Recurrent Oral Ulceration (aphthous or herpetiform) observed by the physician or patient recurring at least 3 times in one 12-month period

Plus at least 2 of the following criteria:

SUBMIT
International Study Group for Behçet's Disease. Lancet. 1990;335:1078-1080.
You have reached the end of the learning module section on
“Recognizing and Diagnosing Behçet’s Disease.”

Thank you for your time and attention.

Please fill out a brief survey below.
1
I am a:
Specialty:
2
Please rate your level of agreement with the following statement:
This section of the learning module improved or reaffirmed my understanding of the signs and symptoms of Behçet’s Disease.
(1=strongly disagree)
(5=strongly agree)
SUBMIT
Learn More About Behçet’s Disease

Learn more about another topic:

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This learning module is intended for healthcare professionals in the United States only.

The Burden of Behçet’s Disease
Check Your Knowledge
Rank the following diseases in order from least to most
significant negative impact on health-related QoL:
(Drag and drop the correct answers into the fields below.)
general population
Type 2 Diabetes
COPD
Active Arthritis
Ischemic Heart Disease
Behçet’s Disease
1
2
3
4
5
6
SUBMIT
COPD, chronic obstructive pulmonary disease; QoL, quality of life.
*Cross-sectional postal survey study of 362 patients with Behçet’s Disease who were members of the Behçet Syndrome Society in the United Kingdom.

COPD, chronic obstructive pulmonary disease; EQ-5D, European Quality of Life 5-Dimension Questionnaire; OA, osteoarthritis; QoL, quality of life.

Bernabé E et al. Rheumatology (Oxford). 2010;49(11):2165-2171.

Patients With Behçet’s Disease Experience Significantly Impaired QoL1
  • Patients with Behçet’s Disease have significantly impaired QoL due to1,*:
pain/
discomfort
Fatigue
Problems
with mobility
Difficulty performing
usual activities
Sleep
disturbances
QoL is impacted by the type and number of symptoms as well as disease activity1
See QoL data for patients
with Behçet’s Disease
*Across multiple measures of QoL, including SF-36, WHOQOL-100, and EQ-5D.2,3

EQ-5D, European Quality of Life 5-Dimension Questionnaire; QoL, quality of life; SF-36, Short-form-36; WHOQoL-100, World Health Organization Quality of Life assessment.

References: 1. Canpolat Ö, Yurtsever S. Asian Nurs Res (Korean Soc Nurs Sci). 2011;5(4):229-235. 2. Ertam I et al. Clin Exp Rheumatol. 2009;27(2 suppl 53):S18-S22. 3. Bernabé E et al. Rheumatology (Oxford). 2010;49(11):2165-2171.

Clinical Symptoms of Behçet’s Disease May
Also Have a Psychological Impact on Patients
Clinical Symptoms of Behçet’s Disease May Have Numerous Psychosocial
and Cognitive Impacts That Contribute to Impaired QoL

  • Low self-esteem
  • Negative effect on body image due to scarring
  • Pain in the body may cause depression, anxiety, fear, tension, and loss of concentration
  • Negative effect on sexual function
  • Negative effect on social relationships
  • Difficulty in fulfilling roles and obligations due to pain in the body and limitation of daily activities

QoL, quality of life.

Canpolat Ö, Yurtsever S. Asian Nurs Res (Korean Soc Nurs Sci). 2011;5(4):229-235.

Diminished Oral Health in Behçet's Disease Has
Debilitating Effects on Daily Function and Overall Quality of Life


*Cross-sectional study in which clinical examinations and questionnaires assessing both oral and general QoL were conducted on 94 patients with Behçet’s Disease, 24 patients with RAS, 113 healthy controls, and 44 dental patients.

BD, Behçet’s Disease; BDCAF, Behçet’s Disease Current Activity Form; HC, healthy controls; OHIP-14, Oral Health Impact Profile-14; OHQoL, oral health quality of life; RAS, recurrent aphthous stomatitis.

References: 1. Mumcu G et al. Oral Dis. 2006;12(2):145-151; 2. Senusi A et al. Rheumatol Int. 2018;38(10):1873-1883.

Check Your Knowledge
On average, how many times will patients with
Behçet’s Disease experience oral ulcers in 1 year?
(Slide the button to select a number.)


Annual Recurrence of Oral Ulcers in Patients With Behçet’s Disease
SUBMIT
Check Your Knowledge
On average, how many times will patients with
Behçet’s Disease experience oral ulcers in 1 year?
  • Due to their severity and recurrence, oral ulcers can interfere with everyday functions like eating and performing oral hygiene3
  • Oral ulcers in patients with Behçet’s Disease take longer to heal than those occurring in patients with RAS (mean healing time of 8.1 ± 2.3 days versus 6.1 ± 1.6 days, respectively; P=0.003)4,††
*In patients who had 2 or more manifestations. †In progressive cases. ‡Retrospective study in Korea of 572 patients who had 2 or more overt manifestations of Behçet’s Disease. §Prospective study of 67 patients with a history of only recurrent oral ulcers registered at the Behçet’s Disease Specialty Clinic at Severance Hospital of Yonsei University, Seoul, Korea. **Cross-sectional study in Japan of 675 patients with Behçet’s Disease. ††Cross-sectional study where clinical examinations and questionnaires assessing both oral and general QoL were conducted on 94 patients with Behçet’s Disease, 24 patients with RAS, 113 healthy controls, and 44 dental patients.

References: 1. Bang D et al. J Dermatol. 1995;22:926-929. 2. Naito M et al. Genet Res Int. 2014;2014:930348. 3. Senusi A et al. Rheumatol Int. 2018;38:1873-1883. 4. Mumcu G et al. Oral Dis. 2006;12:145-151.

Some Clinical Symptoms of Behçet’s Disease Can
Significantly Impact Morbidity and Mortality
(Click on the plus buttons to learn more.)
Ocular, vascular, nervous system, and GI symptoms are closely
correlated with morbidity and mortality IN BEHÇET'S DISEASE1
GI, gastrointestinal.

Cho SB et al. Yonsei Med J. 2012;53(1):35-42.

Some Clinical Symptoms of Behçet’s Disease Can
Significantly Impact Morbidity and Mortality


A survey of 20-year outcomes in a cohort of patients with
Behçet’s Disease (n=387) reported an overall mortality of 9.8%,
primarily due to major vessel disease and neurological involvement*


*Outcome information was collected for 387 of 428 patients in a cohort of patients registered between July 1977 and December 1983 in the multidisciplinary Behçet’s Disease outpatient clinic at Cerrahpaşa Medical Faculty of Istanbul University.

Kural-Seyahi E et al. Medicine (Baltimore). 2003;82(1):60-76.

You have reached the end of the learning module section on
“The Burden of Behçet’s Disease.”

Thank you for your time and attention.

Please fill out a brief survey below.
1
I am a:
Specialty:
2
Please rate your level of agreement with the following statement:
This section of the learning module improved or reaffirmed my understanding of the signs and symptoms of Behçet’s Disease.
(1=strongly disagree)
(5=strongly agree)
SUBMIT
Learn More About Behçet’s Disease

Learn more about another topic:

Home
Review this topic again

This learning module is intended for healthcare professionals in the United States only.