INTRODUCTION:

Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful mouth sores, genital sores, inflammation of parts of the eye, and arthritis. The sores typically last a few days. Less commonly there may be inflammation of the brain or spinal cord, blood clots, aneurysms, or blindness.

Symptoms of Behçet's syndrome depend on the body areas affected including: Arteries that supply blood to the body's tissues, Veins that take the blood back to the lungs, The back of the eyes (retina), Brain, Joints, Skin and Bowels [2][4]

HISTORY:

· The first modern formal description of the symptoms was made by H. Planner and F. Remenovsky and published in 1922 in the Archiv für Dermatologie und Syphilis.

· Behçet's disease is named after Hulusi Behçet(1889–1948)

· The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva in September 1947. Symptoms of this disease may have been described by Hippocrates in the 5th century BC

· The current World Health Organization/ICD-10 standard is "Behçet's disease". In 1991, Saudi Arabian medical researchers described neuro-Behçet's disease^,a neurological involvement in Behçet's disease, considered one of the most devastating manifestations of the disease. The mechanism can be immune-mediated or thrombotic. The term dates back to at least 1990. [1]

INCIDENCE IN INDIA:

Behcet's disease is a chronic, recurrent, multi-systemic inflammatory disorder of unknown aetiology, characterized by the triad of oral ulcers, genital ulcers, and ocular lesions. It appears that either the disease is uncommon, under-diagnosed or under-reported in India. According to the American Behçet's Disease Association, the prevalence of Behcet's disease in Turkey is as high as 400 cases per 100,000 people. [1]

EPIDEMIOLOGY:

It is rare in the United States, Africa and South America, but is common in the Middle East and Asia, suggesting a possible cause endemic to those tropical areas.

· A theory suggested that past exposure to lethal infectious agents might have fixed the genetic susceptibility factors to Behçet's disease in those area^.An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people^.Globally, males are affected more frequently than females

· In an epidemiologic study, 56 percent of patients with Behçet's disease developed ocular involvement at a mean age of 30. Ocular involvement was the first manifestation of Behçet's disease in 8.6 percent of patients. Ocular Behçet's disease with involvement of the optic nerve is rarely reported. Among patients with ocular Behçet's disease funduscopic findings of optic atrophy, and optic disc paleness have been identified with a frequency of 17.9 percent and 7.4 percent, respectively. Other fundoscopic findings include vascular sheathing (23.7%)^,retinal hemorrhage (9%)^,macular edema (11.3%), branch retinal vein occlusion (5.8%), and retinal edema (6.6%). However, optic atrophy was the most significant cause of visual impairment identified in 54 percent of patients with ocular Behçet's disease and permanent visual impairment.

· The prevalence of this disease increases from North to South. It follows a more severe course in patients with an early age of onset particularly in patients with eye and gastrointestinal involvement. [11][12][14]

OTHER NAMES:

· Behçet's syndrome

· Morbus Behçet

· Behçet-Adamantiades syndrome

· Silk Road Disease (While previous research has suggested that ancient travelers on the Silk Road carried diseases such as bubonic plague, anthrax and leprosy, there was little concrete evidence to prove that this occurred)

CAUSES:

· It is primarily characterized by auto-inflammation of the blood vessels

· The primary mechanism of the damage is autoimmune, which by definition is an overactive immune system that targets the patient's own body. The involvement of a subset of T cells (Th17) seems to be important.

· There does however seem to be a genetic component involved, as first degree relatives of the affected patients are often affected in more than the expected proportion for the general population.

· Heat shock proteins (HSPs) are present in some bacteria and serve as a "danger signal" to the immune system. However, some HSPs share a similarity in bacteria and humans.^[13] The anti-HSP60 and anti-HSP65 antibodies that target HSPs produced by Streptococci (including S. sanguinis and S. pyogenes) and Mycobacterium tuberculosis can also target human HSPs, leading to immune responses linked to uveitis and various symptoms shown in parenchymal neuro-Behçet's disease

· GIMAP ("GTPase of the immunity-associated protein") family of genes on the long arm of chromosome 7 has been reported. The genes implicated were GIMAP1, GIMAP2 and GIMAP4.

· Genetic cause [12][14]

PATOPHYSIOLOGY:

A large number of serological studies show a linkage between the disease and HLA-B51. HLA-B51 tends not to be found in disease when a certain SUMO4 gene variant is involved, and symptoms appear to be milder when HLA-B27 is present. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçet's disease, but certain strains of S. sanguinis has been found to have a homologous antigenicity.

Vasculitis resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behçet's disease. Histological evaluation in a reported case of acute optic neuropathy demonstrated substitution of the axonal portion of the optic nerve with fibrous astrocytes without retinal changes. CNS involvement in Behçet's disease may lead to intracranial hypertension most commonly due to dural venous sinus thrombosis and subsequent secondary optic atrophy [5][6][13]

SIGNS AND SYMPTOMS:

· Skin and mucosa: Aphthous ulcers or non-scarring oral lesions. Painful genital ulcerations usually develop around the anus, vulva, or scrotum , erythema nodosum, cutaneous pustular vasculitis, and lesions similar to pyoderma gangrenosum.

· Eyes: Hypopyon which can be seen in anterior uveitis, permanent vision loss,ocular involvement can be in the form of posterior uveitis, anterior uveitis, or retinal vasculitis. Anterior uveitis presents with painful eyes, conjuctival redness, hypopyon, and decreased visual acuity, while posterior uveitis presents with painless decreased visual acuity and visual field floaters. Progressive optic atrophy and visual loss. However, cases of acute optic neuropathy (specifically anterior ischemic optic neuropathy) have also been reported to occur. Optic nerve atrophy has been identified as the most common cause of visual impairment. Papilledema as a result of dural sinus thrombosis and atrophy resulting from retinal disease, have been characterized as secondary causes of optic nerve atrophy in Behçet's disease. Progressive optic atrophy may result in decreased visual acuity or color vision. Intracranial hypertension with papilledema may be present.

· GI Manifestations: Abdominal pain, nausea, and diarrhea with or without blood, and they often involve the ileocecal valve. Many patients with BD often complain about abdominal tenderness, bloating, and generic abdominal discomfort that closely mimics irritable bowel syndrome.

· Lungs: Lung involvement is typically in the form of hemoptysis, pleuritis, cough, or fever, and in severe cases can be life-threatening if the outlet pulmonary artery develops an aneurysm which ruptures causing severe vascular collapse and death from bleeding in the lungs. Nodules, consolidations, cavities and ground glass lesions are common in patients with pulmonary involvement. Pulmonary artery thrombosis may occur.

· Joints: Arthritis is seen in up to half of people, and is usually a non-erosive poly or oligo arthritis primarily of the large joints of the lower extremities.

· Brain: Neuro-Behçet's disease, CNS involvement most often occurs as a chronic meningoencephalitis. Lesions tend to occur in the brainstem, the basal ganglia and deep hemispheric white matter and may resemble those of MS. Brainstem atrophy is seen in chronic cases. Neurological involvements range from aseptic meningitis to vascular thrombosis such as dural sinus thrombosis and organic brain syndrome manifesting with confusion, seizures, and memory loss. Sudden hearing loss (Sensorineural) is often associated with it. s.

· Heart: Pericarditis is a frequent cardiac manifestation. Chronic aortic regurgitation due to aortic root disease may also be seen.

· Blood vessels: Blood vessel problems are observed in 7–29% of people with arterial lesions representing 15% of vascular lesions. Arterial lesions pose a greater risk. Most common arterial lesions are occlusions or stenosis and aneurysms or pseudoaneurysms.

· Symptoms may last for a long time, or they might go away within a few weeks. In most cases, symptoms come and go over long periods of time. When the symptoms are active, this is called a disease flare.

· Pregnancy: With Behçet's disease as an intercurrent disease in pregnancy, the pregnancy does not have an adverse effect on the course of Behçet's disease and may possibly ameliorate its course. Still, there is a substantial variability in clinical course between patients and even for different pregnancies in the same patient. Also, the other way around, Behçet's disease confers an increased risk of pregnancy complications, miscarriage and Cesarean section.

Behçet's can cause male infertility, either as a result of the condition itself or of a side effect of concomitant medication such as Colchicine, which is known to lower sperm count.[7][9]

DIAGNOSTIC EVALUATION:

· A person, he or she has mouth sores at least 3 times in 12 months and any 2 of the following: genital sores, eye inflammation, certain skin lesions, or a positive pathergy or “skin prick” test, in which a doctor sticks the forearm with a tiny needle and looks for a small red.

· A positive result indicates the immune system is overreacting to a minor injury. Although a positive pathergy test is helpful in the diagnosis of Behcet's Disease, only a minority of Behcet's patients demonstrate the pathergy phenomenon by having a positive test.

· Behçet's disease has a high degree of resemblance to diseases that cause mu7cocutaneous lesions such as Herpes simplex labialis, and therefore clinical suspicion should be maintained until all the common causes of oral lesions are ruled out from the differential diagnosis.

· Visual acuity, or color vision loss with concurrent mucocutaneous lesions or systemic Behçet's diseas

· Inflammatory markers such ESR, and CRP may be elevated.

· Optic nerve enhancement may be identified on Magnetic Resonance Imaging (MRI) in some patients with acute optic neuropathy. Cerebrospinal fluid (CSF) analysis may demonstrate elevated protein level with or without pleocytosis.

· A complete ophthalmic examination may include a slit lamp examination, optical coherence tomography to detect nerve loss, visual field examinations, fundoscopic examination to assess optic disc atrophy and retinal disease, fundoscopic angiography, and visual evoked potentials, which may demonstrate increased latency.

· MRI: Demonstrating occlusion of the left sigmoid and transverse sinuses

· Imaging including angiography may be indicated to identify dural venous sinus

· Other symptoms : Arthritis/arthralgia, cardio-vascular problems of an inflammatory origin, changes of personality, psychoses , deep vein thrombosis , epididymitis, extreme exhaustion, inflammatory problems in chest and lungs, mouth ulcers, nervous system symptoms, problems with hearing or balance, stomach or bowel inflammation, superficial thrombophlebitis, any other members of the family with a diagnosis of Behçet's disease.[3][13]

TREATMENT:

· Immunosuppressive medication such as corticosteroids and lifestyle changes. Lidocaine mouthwash may help with the pain. Colchicine may decrease the frequency of attacks. The condition often improves with the passage of time.

· Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. The quality of the evidence for treating the oral ulcers associated with Behçet's disease, however, is poor

· High-dose corticosteroid therapy is often used for severe disease manifestations. Anti-TNF therapy such as infliximab has shown promise in treating the uveitis associated with the disease. Another Anti-TNF agent, etanercept, may be useful in people with mainly skin and mucosal symptoms.

· Interferon alpha-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers as well as ocular lesions. Azathioprine, when used in combination with interferon alpha-2b also shows promise, and colchicine can be useful for treating some genital ulcers, erythema nodosum, and arthritis.

· Thalidomide has also been used due to its immune-modifying effect. Dapsone and rebamipide have been shown, in small studies, to have beneficial results for mucocutaneous lesions.

· Response to ciclosporin, periocular triamcinolone, and IV methylprednisone followed by oral prednisone has been reported although relapses leading to irreversible visual loss may occur even with treatment.

· Immunosuppressants such as interferon alpha and tumour necrosis factor antagonists may improve though not completely reverse symptoms of ocular Behçet's disease, which may progress over time despite treatment. Posterior involvement, particularly optic nerve involvement, is a poor prognostic indicator. Secondary optic nerve atrophy is frequently irreversible. Lumbar puncture or surgical treatment may be required to prevent optic atrophy in cases of intracranial hypertension refractory to treatment with immunomodulators and steroids.

· IVIG could be a treatment for severe or complicated cases. [6][8]

SURGICAL MANAGEMENT:

· Surgical treatment of arterial manifestations of BD bears many pitfalls, since the obliterative endarteritis of vasa vasorum causes thickening of the medial layer and splitting of elastin fibers.

· Anastomotic pseudoaneurysms are likely to form, as well as pseudoaneurysms at the site of puncture in case of angiography or endovascular treatment; furthermore, early graft occlusion may occur

· Endovascular treatment can be an effective and safe alternative to open surgery, with less postoperative complications, faster recovery time, and reduced need for intensive care, while offering patency rates and procedural success rates comparable with those of surgery. This notwithstanding, long‐term results of endovascular treatment in BD are still to be determined. [10]

PROGNOSIS:

Although there is no cure for Behçet disease, people can usually control symptoms with proper medication, rest, exercise, and a healthy lifestyle. The goal of treatment is to reduce discomfort and prevent serious complications such as disability from arthritis or blindness [14]

REFERENCES:

1. Fleming, Ray (November 2014). "Fast fact about Behçet'sDisease". www.niams.nih.gov. Archived from the original on 13 May 2017. Retrieved 29 May 2017.

2. Ball, Gene V.; Fessler, Barri J.; Jr, Bridges (2014). Oxford Textbook of Vasculitis (3 ed.). OUP Oxford. p. 491. ISBN 9780191667022. Archived from the original on 10 September 2017.

3. Bolster MB (2009). MKSAP 15 Medical Knowledge Self-Assessment Program: Rheumatology. Philadelphia, Pa: American College of Physicians. ISBN 978-1-934465-30-1.

4. Eye (7 January 2011). "Access: A case of anterior ischemic optic neuropathy associated with Behçet's disease: Eye". Eye. Nature.com. 25 (3): 395–396. doi:10.1038/eye.2010.208. PMID 21212799

5. Fujikado T, Imagawa K (1994). "Dural sinus thrombosis in Behçet's disease--a case report". Jpn. J. Ophthalmol. 38 (4): 411–6. PMID 7723211.

6. Ozdal PC, Ortaç S, Taşkintuna I, Firat E (2002). "Posterior segment involvement in ocular Behçet's disease". Eur J Ophthalmol. 12(5): 424–31. doi:10.1177/112067210201200514. PMID 12474927.

7. Kansu T, Kirkali P, Kansu E, Zileli T (December 1989). "Optic neuropathy in Behçet's disease". J Clin Neuroophthalmol. 9 (4): 277–80. PMID 2531168.

8. Hatemi G, Seyahi E, Fresko I, Hamuryudan V (2012) Behçet's syndrome: a critical digest of the recent literature. Clin Exp Rheumatol

9. Adam C. Ring (23 August 2012). Steven S. Agabegi; Elizabeth Agabegi (eds.). Step-up to medicine (3rd ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. p. 266. ISBN 978-1-60913-360-3.

10. Genadiev, Genadi Georgiev; Mortola, Lorenzo; Arzedi, Roberta; Deiana, Giuseppe; Spanu, Francesco; Camparini, Stefano (2017). "Surgical Treatment of Angio‐Behçet". Behcet's Disease. InTech. doi:10.5772/intechopen.68664. ISBN 978-953-51-3225-7. Archivedfrom the original on 10 July 2017.

11. "Behcet Disease: Overview – eMedicine Dermatology". Archivedfrom the original on 16 February 2009. Retrieved 28 March 2009.

12. Direskeneli, H. (2013). "Innate and Adaptive Responses to Heat Shock Proteins in Behcet's Disease". Genetics Research International. 2013: 249157. doi:10.1155/2013/249157. ISSN 2090-3154. PMC 3893747. PMID 24490075.

13. Tanaka, T.; Yamakawa, N.; Koike, N.; Suzuki, J.; Mizuno, F.; Usui, M. (June 1999). "Behçet's disease and antibody titers to various heat-shock protein 60s". Ocular Immunology and Inflammation. 7 (2): 69-74. doi:10.1076/ocii.7.2.69.4018. ISSN 0927-3948. PMID 10420201.

14. "Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease". Annals of the Rheumatic Diseases. 72 (9): 1510–6. doi:10.1136/annrheumdis-2011-200288. PMID 23041938

Received on 19.04.2020 Modified on 30.04.2020

Int. J. Nur. Edu. and Research. 2020; 8(3):383-387.

DOI: 10.5958/2454-2660.2020.00082.4