Adamantiades-Behçet's disease.

The multisystem inflammatory disease of chronic nature, known as Behcet's disease (named after the Turkish dermatologist who described its three main symptoms), has another eponymous name - Adamantiades-Behcet syndrome or disease, which records the name of the Greek ophthalmologist who made a great contribution to the study of this disease and its diagnosis.

But the officially approved WHO name is Behcet's disease (ICD-10 code - M35.2). [ 1 ]

Epidemiology

According to global clinical statistics, the prevalence of Adamantiades-Behcet's disease per 100,000 people is estimated at 0.6 cases in the UK, 2.3 cases in Germany; 4.9 in Sweden; 5.2 in the USA; 7 in France; 13.5 in Japan; 20 in Saudi Arabia; 421 in Turkey. [ 2 ], [ 3 ]

Moreover, among patients, men aged 25-40 years predominate, but in the USA, China and northern European regions, the disease is more often detected in women. [ 4 ]

Younger patients have a more severe course of the disease. [ 5 ]

Causes Adamantiades-Behçet's disease.

Although the exact causes of Adamantiades-Behcet disease are not clearly defined, its etiological connection with the autoimmune inflammation of the walls of blood vessels that affects the eyes, skin and other organs – systemic vasculitis – is indisputable. [ 6 ]

According to the traditional international classification of systemic vasculitis (based on the size of the predominantly affected blood vessels), Behçet's disease is a vasculitis that affects the endothelium - the inner lining of arterial and venous vessels of any size and type, causing their occlusion. [ 7 ]

Read more in the publications:

• Behcet's disease in adults
• Behcet's disease in children

Risk factors

Direct risk factors for the development of Behcet's disease (Adamantiades-Behcet's disease) are genetic factors, that is, caused by the predisposition of carriers of certain genes.

In particular, among residents of Middle Eastern and Asian countries, the risk of developing this disease is increased in people with a mutation in the gene that controls the human leukocyte antigen HLA B51 and is associated with hyperreactivity of leukocyte neutrophils - mature blood phagocytes that migrate through blood vessels to the site of inflammation. [ 8 ], [ 9 ]

Also related to vasculitis are changes in genes encoding proteins that participate in autoimmune and inflammatory reactions: tumor necrosis factor (TNF α), macrophage proteins (MIP-1β) and extracellular heat shock proteins (HSP and αβ-crystallin). [ 10 ], [ 11 ]

The following infections cannot be ruled out as triggers: Staphylococcus aureus, Streptococcus sanguis, HSV-1 (herpes simplex virus type I), etc., which cause an autoinflammatory reaction in genetically predisposed people - with an increased level of antiviral antibodies IgG and general immune overexpression. [ 12 ]

Read also: What causes systemic vasculitis?

Pathogenesis

The mechanism of vascular damage and systemic inflammatory manifestations in this disease continues to be the subject of study, but most researchers are confident that the pathogenesis of Behcet's disease is immune-mediated. [ 13 ]

Three possible options are being considered:

• deposition of immune complexes (molecules of antigens bound to antibodies) in the endothelium;
• humoral immune response mediated by antibodies that are secreted by plasma cells and circulate throughout the body (binding to exogenous and endogenous antigens);
• cell-mediated T-lymphocyte response – with increased activity of tumor necrosis factor (TNF-α) and/or macrophage inflammatory protein (MIP-1β). [ 14 ]

As a result of the action of one of the indicated mechanisms, there is an increase in the level of proinflammatory cytokines, activation of macrophages and chemotaxis of neutrophils, which leads to dysfunction of endothelial cells (in the form of their swelling), autoimmune inflammation of the walls of blood vessels with their subsequent obstruction and tissue ischemia. [ 15 ], [ 16 ]

Symptoms Adamantiades-Behçet's disease.

Adamantiades-Behcet disease occurs in attacks, clinical symptoms are complex, and the first signs appear in patients depending on the location of the lesion.

Almost all patients develop multiple painful ulcers in the oral cavity at the initial stage, which may spontaneously heal without leaving scars.

Eight out of ten patients also have recurrent genital ulcers (scrotum, vulva, vagina).

Skin symptoms include erythema nodosum on the lower extremities, pyoderma, acne, and inflammation of the hair follicles.

In half of the cases, ophthalmological manifestations occur in the form of recurrent bilateral uveitis (usually anterior) - with hyperemia of the conjunctiva and iris, increased intraocular pressure, and accumulation of pus in the lower parts of the anterior chamber of the eye (hypopyon). [ 17 ]

Joint lesions (knees, ankles, elbows, wrists) include inflammatory arthritis (without deformities), polyarthritis or oligoarthritis.

The most common manifestation from the vascular system is deep and superficial thrombophlebitis of the lower extremities; an aneurysm of the pulmonary or coronary artery may form, and blockage of the hepatic veins may also occur. A fairly common cardiac manifestation of the disease is inflammation of the pericardium. [ 18 ]

Gastrointestinal lesions include ulcers of the intestinal mucosa. If the lungs are affected, patients experience cough and hemoptysis, and pleurisy may develop. [ 19 ], [ 20 ]

From the side of the central nervous system, lesions are observed in 5-10% of cases of Behcet's disease, and most often the brainstem is affected, causing gait and motor coordination disorders, problems with hearing and speech, headaches, [ 21 ] decreased tactile sensitivity, etc. [ 22 ]

Complications and consequences

In addition to increased mortality (the risk of death increases with the rupture of a pulmonary or coronary artery aneurysm), this disease can cause serious complications and have lifelong negative consequences.

Eye damage in the form of uveitis can be complicated by persistent opacity of the vitreous body, resulting in blindness. [ 23 ]

Clinical manifestations of cardiac complications may include shortness of breath, chest pain, fever.

Intestinal ulcers may lead to perforation, lung lesions may lead to pulmonary artery thrombosis, and CNS lesions may lead to severe neurological deficits.

Diagnostics Adamantiades-Behçet's disease.

Diagnosis of Adamantiades-Behcet disease is clinical and includes examination of the oral cavity, skin, and ophthalmological examination.

The diagnosis is based on three signs, including: the presence of mouth ulcers, eye inflammation, genital ulcers and skin lesions.

Blood tests are taken: general, for inflammation markers, for IgM autoantibodies (rheumatoid factor) and IgG antibodies, for CIC (circulating immune complexes). To confirm the dermatological diagnosis, a biopsy of the affected skin areas is performed. [ 24 ]

Instrumental diagnostics are aimed at examining the affected organs and may include angiography, X-rays of the joints or lungs, computed tomography and magnetic resonance imaging. [ 25 ]

Differential diagnosis

Particularly difficult is differential diagnosis, which must exclude aphthous stomatitis, herpes vulgaris, reactive arthritis, ulcerative colitis and all inflammatory bowel diseases, systemic lupus, urethritis, and other systemic vasculitis. [ 26 ], [ 27 ]

Treatment Adamantiades-Behçet's disease.

Treatment is prescribed taking into account the nature of the lesion and the clinical picture. [ 28 ]

Today, a fairly wide range of pharmacological drugs is used, in particular:

• local or systemic glucocorticoids (Prednisolone, Methylprednisone, Triamcinolone);
• NSAIDs (non-steroidal anti-inflammatory drugs);
• interferon alpha (2a and 2b); [ 29 ]
• Sulfasalazine (Azulfidine),
• Azathioprine (Imuran),
• Colchicine;
• Infliximab and Rituximab; [ 30 ]
• Adalimumab;
• Cyclosporine;
• Cyclophosphamide and Methotrexate;
• Etanercept.

Clinical practice confirms the effectiveness of immunoglobulin therapy for achieving long-term remission: subcutaneously administered synthetic leukocyte interferon. [ 31 ]

Prevention

To date, recommendations for preventing this disease have not been developed.

Forecast

In Adamantiades-Behcet disease, the prognosis is disappointing: this disease is incurable. But in more than 60% of cases, after the active stage of the disease, a long-term remission occurs, and periods of exacerbation are easier.