Adamantiades-Behçet syndrome;

Question 1

Adamantiades-Behçet syndrome:

Definition:

Answer 1

chronic inflammatory multisystemic disorder (with vascular, articular, gastrointestinal, neurologic, urogenital, pulmonary, and cardiac involvement) of unknown etiology with unpredictable exacerbations and remissions

Question 2

Adamantiades-Behçet syndrome:

Etiopathogenesis

Answer 2

• The etiology is unknown
• The most widely accepted theory is that an infectious or environmental
• antigen elicits an abnormal immune response in a genetically susceptible host (presence of HLA-B51 or other susceptibility genes or genetic variations)
• Investigators have correlated attacks to a number of environmental agents, including bacteria (especially streptococci), viruses, pesticides, and heavy metals

Question 3

Adamantiades-Behçet syndrome:

Pathophysiology:

Answer 3

• A clinical hypothesis is that infectious agents and associated stress proteins found in the oral cavity of patients with BD induce cross- reactivity with host cells and stimulate the proliferation of autoreactive T-cell clones
• Heat shock proteins (HSP) can be recognized by pattern recognition receptors to be an endogenous “danger” signal leading to activation of innate and adaptive immune responses. They also increase the expression of adhesion molecules on endothelial cells. Overexpression of pro- inflammatory cytokines, mainly T-helper (Th)1 and Th17 cells appear to be responsible for the enhanced inflammatory reaction. Increased neutrophil activity and neutrophil infiltration in the affected organs may be caused by increased interleukin (IL)-17 response
• The immune system activated at the end of all these complex inflammatory processes is thought to eventually induce tissue damage and vasculitis

Question 4

Adamantiades-Behçet syndrome:

Characteristics:

Answer 4

• Begins between the ages of 20–40
• The course of the disease is more severe in male patients with younger age at onset and an increased number of organs affected at diagnosis
• The disease can be recognized by clinical findings because of the absence of a universally accepted diagnostic laboratory test
• Diagnosis is largely based on mucocutaneous symptoms

Question 5

Adamantiades-Behçet syndrome:

Symptoms:

Answer 5

Question 6

Adamantiades-Behçet syndrome:

Oral ulcers –1st manifestation:

Answer 6

• Recurrent ulcerations of the oral mucosa, clinically indistinguishable from RAS
• Anywhere in the oral cavity, but the most commonly affected sites are the labial and buccal mucosa, tongue, soft palate, and oropharynx
• RAS generally starts as an initial symptom in BD patients since their childhood and/or youth and other mucocutaneous symptoms follow after RAS

Question 7

Adamantiades-Behçet syndrome:

Genital ulcers:

Answer 7

• are rarely the presenting feature of BD.
• The ulcerations may be preceded by a papule or pustule and appear similar to oral aphthae but occur less often and scar more frequently
• Associated pain may cause difficulty with micturition, dyspareunia, and even hinder walking
• In women, ulcers most commonly affect the labia, but lesions in the vaginal mucosa and cervix may also occur
• In men, the scrotum is regularly involved, although involvement of the shaft and glans penis is also frequent
• Ulcers in the groin, perineum, and peri- anal area are seen in both genders

Question 8

Adamantiades-Behçet syndrome:

Ocular lesions:

Answer 8

• Ocular disease is seen in 30–70% of patients and is more frequent and severe in men
• Typically, ocular symptoms begin after the onset of oral ulceration. However, intra- ocular inflammation is the presenting feature in approximately 20% of cases. Ocular disease is bilateral in 85% of patients and runs a relapsing course in 95% of cases
• Panuveitis, posterior uveitis, anterior uveitis, retinal vasculitis, optic neuritis, and retinal vein occlusion are the most common features and cause significant morbidity
• Formation of a hypopyon, a visible layer of pus in the anterior chamber, is seen in 12% of patients and rarely in other conditions

Question 9

Adamantiades-Behçet syndrome:

Cutaneous lesions:

Answer 9

• Skin lesions are described in approximately 80% of patients with BD
• Erythema nodosum-like lesions are seen in 30% of patients, mainly on the lower extremities but also on the face, neck, and buttocks
• Lesions rarely ulcerate, resolve within 2–3 weeks, and can cause post-inflammatory hyperpigmentation
• While clinically similar to classical erythema nodosum, lesions of BD differ histologically, with evidence of vasculitis (Kim and LeBoit 2000)
• Other common skin lesions include papulopustular lesions, acneiform, superficial thrombophlebitis, pyoderma gangrenosum- like lesions, and pathergy

Question 10

Adamantiades-Behçet syndrome:

Musculoskeletal Manifestations:

Answer 10

• Inflammatory, non-erosive, non-deforming arthritis is seen in 50% of patients with Behcet disease, more common in patients with acneiform lesions
• It is usually oligoarthritis that is symmetric or asymmetric, but polyarthritis and monoarthritis can also be seen joint involvement is peripheral, and spine involvement or sacroiliitis is not usually seen, differentiating it from HLA- B27 associated erosive sacroiliitis
• Knees are the most commonly involved joint, followed by ankles, wrists, and elbows

Question 11

Adamantiades-Behçet syndrome:

Mucocutaneous lesions of Behçet’s disease:

Answer 11

1. Oral ulcers on the uvula with rolled borders and a grayish yellow necrotic base, and numerous scars on the soft palate from the previous ulcers
2. Genital ulcers are similar in appearance and course to oral ulcers; the scrotum is the most commonly involved site in males
3. Erythema nodosum-like pretibial, painful and erythematous nodules
4. Papulopustular lesions are folliculitis- or acne-like lesions on an erythematous base which appear as a papule and in the course of 24–48 h become a pustule
5. Superficial thrombophlebitis erythematous, tender subcutaneous nodules arranged in a linear fashion
6. Skin pathergy test; positivity is defined as the development of a papule or pustule at the needle-prick site after 24–48 h

Question 12

Adamantiades-Behçet syndrome:

Pathergy:

Answer 12

Pathergy is an exaggerated skin injury occurring after minor trauma such as bump, bruise, needle stick injury

Question 13

Adamantiades-Behçet syndrome:

What is the skin pathergy test?

Answer 13

• Multiple pricks are made into the forearm, using a sterile needle. The pricked area is observed over the next 24 to 48 hours
• Positive pathergy tests are present if a papule or pustule or ulceration are observed at the site of the needle prick
• Pathergy test is done both orally and cutaneous
• Orally lower lip is the site of testing.
• Appearance of any ulcer or papule indicates positive pathergy reaction

Question 14

Adamantiades-Behçet syndrome:

Diagnosis:

Answer 14

The International Study Group for Behçet’s disease criteria, is the most commonly used and internationally recognized diagnostic criteria requires the presence of oral ulcer plus any two of recurrent genital ulcer, typical eye lesions, typical cutaneous lesions, or a positive skin pathergy test

• Is clinical and can be difficult due to the lack of any pathognomic laboratory finding
• Laboratory findings are usually non-specific, including anemia of chronic disease, leukocytosis, and elevation in markers of inflammation
• Imaging studies shall be directed at the organ involved and may include X-rays and arthrocentesis to assess arthritis, CT-scan to assess for bleeding, thrombosis, and ischemia, angiography to look for aneurysms and lumbar puncture to evaluate meningitis
• The rationale for carrying out these investigations is to rule out other causes of the clinical presentation
• A careful ophthalmologic examination to evaluate ocular involvement shall be pursued at initial presentation, and cutaneous lesions shall be biopsied to confirm the cutaneous diagnosis

Question 15

Adamantiades-Behçet syndrome:

Management:

Answer 15

• No curative therapy is currently available for BD
• The ultimate goals of treatment are to prevent irreversible organ damage, which occurs especially in the early stage and active phases of the disease, and to alleviate symptoms
• Mucocutaneous involvement:
• No curative therapy
• Topical corticosteroids, lidocaine containing creams, or sucralfate suspension can be used for most minor orogenital lesions
• For severe or refractory mucocutaneous lesions, colchicine, dapsone, thalidomide, methotrexate, prednisone, or interferon-alpha can be considered
• As for RAS, the treatment of oral ulcers and other mucocutaneous lesions consists mainly in the use of topical agents, particularly steroids