Critical review

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Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Vallianou NG, Panagos J. Adamantiades-Behcet’s disease: the past, the present and the future. OA Arthritis 2013 Jun 01;1(2):13. Co

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AbstractIntroductionAdamantiades-Behcet’s disease is more common along the ‘Silky Road’ and among young adults with HLA-B51 allele. The aim of this review was to discuss the past, present and future of Adamantiades-Behcet’s disease.Discussion It is a chronic relapsing vasculitis characterised by recurrent oral and genital ulcers, cutaneous and ocular manifestations. Visual loss may occur in up to 20% of the affected patients. Arthritis, gastrointestinal and nerv-ous involvement may occur. This vas-culitis has a tendency for superficial and deep vein thrombosis.

Corticosteroids remain the main-stay of treatment, while other immunosuppressive agents, such as azathioprine, cyclophosphamide, anti-TNF-a, colchicine and thalido-mide have been used successfully for its treatment. Anti-TNF-a agents seem to be very promising for severe central nervous system, ocular and gastrointestinal involvement.ConclusionMorbidity is mainly due to ocular lesions, while mortality is low and is due to CNS involvement, bowel per-foration, pulmonary symptoms or thrombosis.

IntroductionThe first description of Adamantia-des-Behcet’s disease was attributed to Hippocrates in the fifth century BC. In 1931, the Greek opthalmologist

Benediktos Adamantiades described a patient with relapsing iritis and hypopyon and associated other clini-cal features such as: genital ulcers and arthritis as features of a single disease1. In 1937, the Turk opthal-mologist Hulusi Behcet reported the classical triad of oral and genital ulcer-ation together with ocular inflamma-tion in a small number of patients2. Adamantiades-Behcet’s disease is a multisystem, inflammatory disorder of unclear aetiology that is charac-terised by recurrent oral ulcers and two of the following: genital ulcers, skin lesions, a positive pathergy test and ocular involvement3,4. Other manifestations include arthritis, thrombophlebitis, central nervous system disease and gastrointestinal ulcerations5–10. This review discusses Adamantiades-Behcet’s disease.

Clinical presentationAdamantiades-Behcet’s disease is most common along the areas crossed by the ‘Silk Route’ countries, from the Mediterranean sea to the Far East11,12. Genetic factors known to be involved is the HLA-B51 allele, while environ-mental stimuli seem to participate in the initiation of symptoms among young adults13. Cytokines, such as interleukin-1, interleukin-8, interleu-kin-17, TNF-a, heat shock proteins, macrophage activation and neutro-phils chemotaxis seem to be involved in the pathogenesis of the disease.

Adamantiades-Behcet’s disease is a chronic, multisystem relapsing vasculitis that presents predomi-nantly with recurrent oral and geni-tal ulcers, skin lesions and ocular involvement. International criteria have been established for its diagno-sis, which have a sensitivity of 85%

and a specificity of 96%. These crite-ria include recurrent oral ulcers and at least two of the following: recurrent genital ulceration, eye lesions, skin lesions and pathergy test. These crite-ria are applicable only in the absence of other possible explanations14. Oral ulcers are painful lesions with round, sharp, erythematous and elevated borders, which may appear on the tongue, pharynx, buccal and labial mucosal surfaces. They may start as a raised redness, around 1–3 cm and they may soon ulcerate. The surface is covered with a yellow-ish pseudomembrane. The lesions heal within about 10 days mostly without scarring. Genital ulcers affect 60%–65% of patients, have the same characteristics with oral ulcers, but are usually larger, deeper and tend to leave scars in 50% of the affected patients15. Skin lesions can be divided into two main types: erythema nodo-sum and papulopustular/acneiform lesions16. The formal pathergy test involves intradermal pricking of the skin with a needle and it is consid-ered positive if an erythematous papule or a pustule develops at the prick site within 48 hours, while the occurrence of a papule or pustule at the site injection is considered as an analog to the formal pathergy test17. Ocular involvement is usually bilat-eral and occurs within the first two to three years of the onset of Adamantiades-Behcet’s disease. The most common ocular manifestations are relapsing remitting posterior uveitis, panuveitis and retinal vasculitis. Less common manifestations include scle-ritis, episcleritis, conjctuval ulcers and extraocular muscle paralysis. Visual loss occurs in up to 25% of the affected patients18. Other manifestations such

Adamantiades-Behcet’s disease: the past, the present and the future

NG Vallianou*, J PanagosRheu

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*Corresponding authorEmail: natalia.vallianou@hotmail.com

Evangelismos General Hospital, Athens, Greece

Critical review

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Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Vallianou NG, Panagos J. Adamantiades-Behcet’s disease: the past, the present and the future. OA Arthritis 2013 Jun 01;1(2):13. Co

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as arthritis, involvement of the gastro-intestinal tract, superficial and deep venous thromboses and brain involve-ment may also occur16.

Gastrointestinal symptoms may include diarrhoea, nausea, abdominal pain and sometimes true perforation. Its distinction from inflammatory bowel disease may be very difficult, even in biopsy specimens. Lesions may be located throughout the gastrointestinal tract, from the oesophagus to the large intestines. Pancreatitis may rarely occur15.

Neurological involvement affects 20%–40% of patients. Usually, it is observed later in the course of Adamantiades-Behcet’s disease, even up to 10 years later19. Central nerv-ous system involvement more often manifests as an attack rather than a mild progressive disease. Head-ache, meningitis, meningoencepha-litis, seizures, hemiplegia or cranial nerve paralysis may occur. Psycho-sis or personality changes may be observed, which may be difficult to differentiate from iatrogenic side effects of therapy20,21. Cerebral venous thrombosis or benign intracranial hypertension is non- parenchymal disorders due to thrombosis22. Multifocal areas of demyelination of

the white matter are a feature of mul-tiple sclerosis, but it can also be seen in Adamantiades-Behcet’s disease with involvement of the central nerv-ous system (Figure 1)23,24.

Arthralgia and/or arthritis of the knees, wrists, elbows and ankles may occur in up to 45% of the cases and it usually precedes years before the other manifestations16. Arthritis is usually non-erosive, inflammatory, symmetric or asymmetric oligoarthritis, although polyarthritis or monoarthritis may rarely occur. Among patients with Adamantiades-Behcet’s disease there is tendency for superficial and deep venous thrombosis, which is associ-ated with this vasculitis. Thrombosis in the dural sinuses, superior and inferior vena cava and Budd–Chiari syndrome carry a poor prognosis25.

Apart from venous thromboembo-lism, arterial involvement has been documented in 2%–3% of the patients. Arterial involvement may be in the form of thrombosis or aneurysms. Other very rare manifestations such as cardiac involvement in the form of

Figure 1: (a) A brain magnetic resonance imaging depicting Neuro-Behcet’s disease with demyelinating lesions. (b) This is a thoracic CT scan of a patient with Adamantiades-Behcet’s disease, who has superior vena cava syndrome due to the tendency of this vasculitis for deep venous thrombosis.

myocarditis, myocardial infarction, endocarditis or pericarditis or pul-monary involvement such as aneu-rysms, infarction, haemorrhage may result in death among patients with Adamantiades-Behcet’s disease. Renal involvement is very rare and may occur as glomerulonephritis. Haematological involvement, such as haemophagocytic syndrome may also occur16.

DiscussionTreatmentCorticosteroids remain the main-stay of treatment in Adamantiades- Behcet’s disease. They can be applied topically or systematically in the cases of Neuro-Behcet’s disease and in cases of ocular involvement. After the initial 1 g methylprednisolone for three days intravenously, cor-ticosteroids may be reduced with caution after four weeks of therapy. Relapses are frequently seen after discontinuation of corticosteroids. Immunosuppressive drugs have been proved to be effective, such as azathioprine, cyclophosphamide,

(B)(A)

Critical review

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Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Vallianou NG, Panagos J. Adamantiades-Behcet’s disease: the past, the present and the future. OA Arthritis 2013 Jun 01;1(2):13. Co

mpe

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cyclosporine, methotrexate and anti-TNF-a agents, the latter especially in cases of severe uveitis, central nervous disease or severe gastroin-testinal involvement26,27. Anti-TNF-a agents seem to be very promising for the severe attacks of Adamantiades-Behcet’s disease27. Plasmapheresis, intravenous immunoglobulins and alpha-interferon have been also effi-cacious in severe cases28. Colchicine and thalidomide have been used suc-cessfully in mucocutaneous symp-toms, together with other agents15,29. Colchicine is usually given at doses of 1–2 mg daily and seems to decrease the frequency and size of mucocuta-neous lesions. Dapsone is helpful for mucocutaneous lesions at a dose of 50–150 mg daily alone or in combi-nation with colchicine. Topical cor-ticosteroids or tacrolimus may also be applied. In severe mucocutaneous disease, which does not respond to topical treatment or colchicine alone or plus dapsone thalidomide may be used. As an alternative, low dose pred-nisone and low dose methotrexate (2.5–25 mg weekly) may be adminis-tered. Furthermore, interferon-a may be used for severe mucocutaneous disease and some systemic manifes-tations at a dose of 9 million units three times weekly initially and after-wards in 3 million units three times weekly as a maintenance therapy.

ConclusionThe main cause of morbidity in Adamantiades-Behcet’s disease is an ocular disease, while mortality is generally low and is attributed to Neuro-Behcet’s disease, pulmonary involvement, thrombosis and bowel perforation.

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