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Syphilis can present with a wide array of symptoms . Primary syphilis presents with a painless genital ulcer (chancre) and local non-tender lymphadenopathy. It can present with painless oral ulcers although this is less common. Secondary syphilis occurs 4-10 weeks after infection and manifests with a non-pruritic rough red/reddish-brown papular rash, typically on the trunk, and flu-like symptoms such as pyrexia, pharyngitis, malaise, arthalgia/myalgia, lymphadenopathy, and headache. There are a wide variety of rare manifestations, hence the nickname "the great imitator", including uveitis, hepatitis, meningitis, glomerulonephritis, periostitis, cranial nerve palsies, and patchy alopecia. The patient in this question does not have any flu-like symptoms or lymphadenopathy and his ulcers are painful, making secondary syphilis less likely
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Secondary syphilis
QuestionChoice
Behçet's disease is a systemic disorder of recurrent acute inflammation. It affects multiple organs, although is primarily characterised by oral ulcers, recurrent genital ulcers (which disappear and recur spontaneously), and anterior uveitis. It can also effect other organ systemic including skin, pulmonary, vascular, gastrointestinal, musculoskeletal, and central nervous systems. It is most common in ages 20-40, predominantly in males, and has greatest prevalence in Eastern Asia and the Mediterranean. There are no specific tests for Behçet's disease although HLA-B51 is the most strongly associated known genetic factor. In this question the patient is describing anterior uveitis, oral and genital ulcers, and arthralgia and so Behçet's disease is the most likely diagnosis
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Behçet's disease
QuestionChoice
Reactive arthritis is an RF-seronegative, HLA-B27-linked inflammatory arthritis that develops in response to a recent infection. It usually develops following gastrointestinal infections such as _Salmonella_, _Shigella_, or _Campylobacter_ or genitourinary infections such as _Chlamydia trachomatis_. It also presents in ages 20-40 and predominantly in males but is characterised by large joint asymmetric inflammatory oligoarthritis, conjunctivitis/uveitis, and urethritis/cervicitis (can't see, pee, or climb a tree). This patient does not complain of dysuria or symptoms of urethritis and so Behçet's disease is more likely. While reactive arthritis can occasionally cause recurrent aphthous ulcers, on balance the patient's symptoms are more in keeping with Behçet's disease
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Reactive arthritis
QuestionChoice
Reactive arthritis is an RF-seronegative, HLA-B27-linked inflammatory arthritis that develops in response to a recent infection. It usually develops following gastrointestinal infections such as _Salmonella_, _Shigella_, or _Campylobacter_ or genitourinary infections such as _Chlamydia trachomatis_. It also presents in ages 20-40 and predominantly in males but is characterised by large joint asymmetric inflammatory oligoarthritis, conjunctivitis/uveitis, and urethritis/cervicitis (can't see, pee, or climb a tree). This patient does not complain of dysuria or symptoms of urethritis and so Behçet's disease is more likely. While reactive arthritis can occasionally cause recurrent aphthous ulcers, on balance the patient's symptoms are more in keeping with Behçet's disease
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Malaria
QuestionChoice
HIV Seroconversion presents 3-12 weeks following initial infection. It presents with a mononucleosis-like illness with symptoms including fever, malaise, lethargy, myalgia, lymphadenopathy, pharyngitis, painful oral/genital ulcers, and/or non-pruritic maculopapular rash. It very rarely presents with anterior uveitis and would not present with on-and-off self-resolving ulcers over 12 months
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HIV seroconversion
QuestionComment
Turkish man with Behçet's. Nice.
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like the Japanese with Takayasu
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subscriber
Sir Pep Guardiola
User
subscriber
Hypertension Sclerosis
QuestionComment
Can't see, breed or climb a tree
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Prolapsed Fissure
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# Summary

Behcet's disease is a chronic systemic inflammatory disease which mainly affects people from the Middle East, the Mediterranean and East Asia. The classic triad of manifestations is with oral and genital ulceration and ocular involvement (e.g. uveitis or retinal vasculitis). The gastrointestinal tract, central nervous system, skin and cardiovascular systems may also be affected. Investigations include blood tests showing raised inflammatory markers during acute attacks, testing for HLA-B51 (the most strongly associated genetic risk factor) and a pathergy test (where minor skin trauma leads to the formation of a skin lesion). Management may be local (e.g. topical steroids for orogenital ulceration) or systemic, which may include steroids or other immunosuppressive treatments such as azathioprine or cyclophosphamide. Complications include aneurysm rupture, ischaemia due to vessel thrombosis, permanent visual loss and cerebral vein thrombosis.

# Definition

Behcet's disease is a rare multisystem inflammatory disease that typically causes mouth and genital ulceration, skin lesions, uveitis and arthralgia. Severe complications may result from pulmonary, cardiovascular or central nervous system involvement (also referred to as neuro-Behcet's disease).

# Epidemiology

- The disease is most common in people from Turkey (approximately 80 to 370 cases per 100,000 people)
- North Africa, the Middle East, South East Asia and other Mediterranean countries also have a relatively high prevalence of cases
- Overall however it is a rare condition, and can affect people of all ethnicities
- Men and women are equally likely to develop Behcet's disease, but men tend to be more severely affected
- HLA-B51 is the most strongly associated genetic risk factor
- Age of onset is usually in the 20s or 30s, although around 20% of cases present in childhood

# Diagnostic Criteria

The **International Criteria for Behcet's Disease** are based on the presence of typical clinical features as follows - a score of 4 or more is indicative of a diagnosis of BehcBehcet'set's disease:

| Clinical feature| Points |
|----------|----------|
| Ocular lesions | 2 |
| Genital aphthosis (painful ulceration) | 2 |
| Oral aphthosis | 2 |
| Skin lesions | 1 |
| Neurological manifestations | 1 |
| Vascular manifestations | 1 |
| Positive pathergy test (optional) | 1|


# Signs and Symptoms

**Systemic** symptoms include:

- Fatigue
- Malaise
- Myalgia
- Low-grade fevers
- Headaches
- Arthralgia (an inflammatory arthritis may also occur)

**Mucocutaneous** signs and symptoms include:

- Recurrent oral ulceration (the most common manifestation)
- Mouth ulcers are usually painful
- They may cause difficulty eating and drinking
- Usually heal within 7-21 days
- Recurrent genital ulceration
- These are very painful
- Usually occur on the scrotum in males, and the vulva and in the vagina in females
- Skin lesions
- Erythema nodosum (painful nodules usually on the legs)
- Acne-like papulopustular or nodular lesions on the limbs
- Pathergy (eruption of papulopustules at the site of minor skin trauma within 24-48 hours)
- Superficial thrombophlebitis (tender subcutaneous nodules overlying the inflamed vein)

**Ocular** manifestations include:

- Uveitis (anterior or posterior)
- The affected eye is red and painful
- Vision is blurred with photophobia
- Visual loss may occur
- Retinal vasculitis may present with sudden visual loss

**Pulmonary** involvement:

- Seen in a minority of people
- Pulmonary arterial aneurysms may form
- These are usually multiple and bilateral
- May be asymptomatic
- May cause dyspnoea, chest pain and cough
- Rupture can lead to haemoptysis, syncope, cardiogenic shock and sudden death 
- Small vessel vasculitis may occur
- Ground glass appearances and/or alveolar haemorrhage may be seen on imaging
- This can also cause haemoptysis, dyspnoea and chest pain
- Pulmonary artery thrombosis may occur
- This causes haemoptysis, dyspnoea and chest pain (i.e. similar to symptoms of a pulmonary embolism)

**Central nervous system** manifestations include:

- Headaches
- Personality changes
- Cerebellar signs
- Dysarthria
- Sensory changes
- Memory loss
- Meningoencephalitis
- Cerebral vein thrombosis
- Presents with headache, decreased consciousness, visual loss and nausea and vomiting
- Signs include papilloedema, focal neurological deficits, seizures and cranial nerve palsies

**Gastrointestinal** (GI) involvement may present with:

- Ulceration causing GI bleeding or perforation
- May cause nausea and vomiting, abdominal pain, anorexia and diarrhoea

**Cardiovascular** involvement may include:

- Deep vein thrombosis (with limb swelling, erythema and tenderness)
- Pericarditis 
- Vasculitis may affect the aorta and superior vena cava
- Coronary artery aneurysms may lead to acute coronary syndrome
- Cardiomyopathy with subsequent heart failure

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# Differential Diagnosis

- **Herpes simplex virus** as a cause of recurrent painful genital and oral ulceration with associated systemic symptoms of malaise 
- **Sarcoidosis** causes similar features of erythema nodosum, arthritis and uveitis and may also affect the lungs and central nervous system, however genital ulcers are not a feature
- **Reactive arthritis** may present with orogenital ulcers and uveitis, although the urethritis and sacroiliitis seen are not typical of Behcet's disease
- **Crohn's disease** often causes oral ulceration, GI symptoms that may affect anywhere in the GI tract (as in Behcet's disease), and extraintestinal features of rashes, arthritis and uveitis may also occur; however genital ulcers and central nervous system features are not seen in Crohn's disease 
- **Systemic lupus erythematosus** shares many features including systemic symptoms, arthritis, central nervous system involvement and ulcers (common in the mouth but rare in the genital area); typical rashes differ from Behcet's disease (e.g. malar rash on the face) and blood tests may show antinuclear, anti-double stranded DNA and/or anti-Smith antibodies

# Investigations

There is no specific diagnostic test for Behcet's disease - investigations may be to rule out differential diagnoses or identify specific organ complications.

**Bedside tests:**

- **Wound swabs** from oral or genital ulcers may be sent for microscopy and/or viral PCR to rule out infectious causes
- **Urinalysis** should be done to look for blood and protein indicating renal involvement which may occur in differentials such as systemic lupus erythematosus

**Blood tests:**

- **FBC** often shows a high white cell count and a mild anaemia of chronic disease
- **CRP** and **ESR** may be raised but can be normal even when disease is active
- **HLA-B51** is not generally useful for diagnosis 
- **Rheumatoid factor**, **ANA** and **ANCA** are typically negative
- **Syphilis serology** as another cause of oral and genital ulceration
- Baseline **U&Es** and **LFTs** prior to starting treatment
- Genetic testing with **next generation sequencing** is increasingly used to rule out monogenetic conditions that may mimic Behcets disease

**Imaging:**

- **MRI head** in neuro-Behcet disease may show parenchymal lesions, most commonly affecting the thalamus, midbrain and internal capsule
- **MR venography** may be done if central venous sinus thrombosis is suspected
- **Angiography** is used to identify and assess aneurysms
- **High-resolution CT chest** may be done in patients with respiratory symptoms to identify pulmonary involvement

**Special tests:**

- A **pathergy test** is non-specific but may be used to support the diagnosis
- A sterile needle is used to make a skin prick
- The area is then reassessed after 24-48 hours 
- The test is positive if there a papule or pustule forms at that site
- It is often positive in pyoderma gangrenosum and acute febrile neutrophilic dermatosis
- It can also be positive in inflammatory bowel disease or in healthy people
- **Lumbar puncture** may be indicated in neuro-Behcet disease 
- e.g. to rule out infective causes of meningoencephalitis
- Elevated cerebrospinal fluid pressure may be seen
- Raised protein, a pleocytosis and absent oligoclonal bands is typical
- **Endoscopy** may be required for investigation of GI symptoms and to rule out inflammatory bowel disease 
- **Biopsy of skin lesions** may show leukocytoclastic vasculitis and panniculitis (inflammation of the subcutaneous fat)

# Management

**Conservative management:**

- Patients should be managed in specialist services, with input from multiple specialities often required for different manifestations
- Prompt management of ocular disease in particular is key to minimise the risk of sight loss
- Physiotherapy, occupational therapy and/or podiatry input may be helpful for joint disease or functional impairment e.g. in neuro-Behcets
- Patients should be educated on the disease and on self-management, for example for mouth ulcers:
- Maintain good oral hygiene
- Attend regular dental appointments
- Use topic antiseptics e.g. chlorhexidine mouthwash
- Avoid foods that cause irritation
- Patients should be regularly assessed for both disease extent, overall disease activity and quality of life 
- Clinical psychology input is key for general emotional support and focused interventions to support self-management and address distress
- Neuropsychology assessment should be carried out for all patients with neuro-Behcets

**Medical management:**

- Systemic steroids with a steroid-sparing agent (e.g. methotrexate or azathioprine) are first-line for ocular Behcets
- Oral and genital ulcers may be treated with potent topical steroids (combined preparations with antibiotics and antifungals are also available)
- Colchicine is a second-line option for mucocutaneous lesions, and the first-line treatment for arthritis and arthralgia
- Second-line treatments for joint disease include intra-articular or oral steroids or NSAIDs
- Gastrointestinal Behcets is managed with similar medications to inflammatory bowel disease, with 5-aminosalicylic acid, azathioprine and 6-mercaptopurine all first line options as well as steroids for flares
- Neuro-Behcets should be treated with high-dose steroids +/- cyclophosphamide or anti-tumour necrosis factor (TNF) biologics
- Patients with deep vein thrombosis should not be anticoagulated due to the risk of adverse effects - steroids and azathioprine or anti-TNF agents are first-line

**Surgical and interventional management:**

- Emergency surgery may be required for complications such as major GI bleeding or perforation
- Stenting or surgery may be required for arterial involvement e.g. aneurysms

# Complications

- Visual loss
- GI bleeding 
- GI perforation
- Acute ischaemia of limbs or organs due to vasculitis or thrombosis
- Acute coronary syndrome
- Aneurysm rupture (e.g. in the lungs or the brain)
- Seizures
- Cognitive impairment is common especially in neuro-Behcets
- Psychological distress including depression and anxiety

# Prognosis

- The typical disease course is with flares of disease with intervening periods of remission
- The disease often becomes less active over time
- Mortality is generally low but is higher in men and patients with an early age of onset
- However death may occur due to neurological, GI or cardiovascular involvement
- Immunosuppressive treatments are also associated with significant risks e.g. of infection 

# References

[Behcets UK Factsheets](https://behcetsuk.org/behcets-medical-factsheets/)

[British Association of Dermatologists and British Society for Rheumatology living guideline](https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae438/7753993)

[The International Criteria for Behcets Disease](https://behcetsuk.org/wp-content/uploads/2018/06/ICBD-New-Criteria-2013.pdf)

[Patient UK - Behcet's Disease](https://patient.info/doctor/behcets-disease-pro)

[Radiopaedia - Behcet's Disease](https://radiopaedia.org/articles/behcet-disease-2?lang=gb)

[DermNet NZ - Behcet's Disease](https://dermnetnz.org/topics/behcet-disease)
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Oral ulcers seen in a patient with Behcet's syndrome.
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Rheumatology
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Behcet's disease
Behçet's disease
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Behçet's disease is an autoimmune disorder characterized by recurrent, painful oral and genital ulcers, anterior uveitis, and systemic inflammation
A 35-year-old Turkish man presents to accident and emergency with painful erythematous sclera and blurred vision of his right eye. He has had something similar in the past however it was not painful and resolved without treatment. 

He also describes 3 episodes of self-terminating painful oral and genital ulcers in the past year and ongoing bilateral arthralgia in his proximal joints.


Observations are normal. On examination, he has a globally erythematous right sclera. Vision is 6/12 in right, 6/6 in left (baseline 6/6 bilaterally). He has four well-circumscribed aphthous ulcers in his oral cavity and two further ulcers on the glans and shaft of his penis.

What is the most likely diagnosis?
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