Please also see the clinical vignette presented during last week’s grand rounds
Dr. Yusuf Yazici of the NYU Behcet’s Syndrome Center opened his talk by discussing the classic triad of symptoms characteristic of Behcet’s Disease: aphthous ulcers, genital ulcers and uveitis. This was originally characterized by the Turkish physician Hulusi Behcet in 1937. While these symptoms are the most common of Behcet’s, other tissues may be affected as Behcet’s is a systemic vasculitic disorder. GI symptoms, neurological sequelae, the pathergy reaction, erythema nodosum, papulopustular acne, and arthritides are all manifestations of Behcet’s Syndrome. There are no pathognomonic laboratory tests or imaging for Behcet’s; the diagnosis is made clinically.
After the initial review of the clinical manifestations and diagnostic strategies for Behcet’s Disease, Dr. Yazici spent some time discussing some of the severe manifestations that cause much of the mortality, namely pulmonary artery aneurysms. He noted that intense immunosuppression has decreased the mortality of this deadly manifestation of Behcet’s from about 80 to 20 percent. However, it was stressed that pulmonary arterial aneurysms are also strongly associated with venous thrombosis. Venous thrombosis and pulmonary arterial aneurysm with hemoptysis can easily be mistaken as manifestations of pulmonary embolism; however, anticoagulation of pulmonary arterial aneurysm is potentially disastrous, creating a serious diagnostic dilemma.
The final clinical expression of Behcet’s described by Dr. Yazici was the pathergy reaction whereby one makes multiple intradermal skin breaks with a 20 gauge needle. Importantly, this test should not break a blood vessel. A positive reaction consists of an intense inflammatory response at the site of at least one injection. This reaction can occur at any epithelial site including the eye and it has been seen as the first manifestation of Behcet’s after minor eye surgery.
Remarkably, the epidemiology of Behcet’s Syndrome follows the genetic distribution of HLA-B51. Geographically this represents the area along the ancient ‘silk road’, which extends from eastern Asia to the Mediterranean. While genetics plays an important role in the etiology of Behcet’s, environmental triggers are also essential. Dr. Yazici noted that while rates of Behcet’s in patients who have left the aforementioned geographies are the same, the manifestations of the disease are less severe elsewhere in the world, suggestive that environmental triggers are important in the Behcet’s Disease.
The differential diagnosis of Behcet’s is markedly varied considering the panopoly of clinical signs; included in the differential are: SLE, IBD, HLA-B27 associated arthropathies, sarcoidosis, familial Mediterranean fever, multiple sclerosis, and systemic infections such as tuberculosis, human immunodeficiency virus, and syphilis.
The prognosis in Behcet’s is worst for young men in endemic areas. The most common causes of death are related to vascular disease and neurological involvement. In terms of treatment, while numerous agents have been tried, there is a general paucity of double-blinded RCTs. Pharmacotherapy has included:
- Colchicine (though results have been mixed, it has been associated with significant reductions in the number of arthritic joints in all patients and in genital ulcers and erythema nodosum in women)
- Glucocorticoids (for patients with severe disease, despite no high-quality placebo-controlled trials)
- Azathioprine (RCTs have shown significant response in mucocutaneous lesions, arthritis and ocular manifestations when used in conjunction with glucocorticoids)
- Cyclophosphamide (though limited data, cyclophosphamide is used most often for neurologic and vascular Behcet’s. )
- Cyclosporine (in combination with glucocorticoids, and sometimes azathioprine it is used to treat ocular, mucocutaneous, and articular disease.)
- Anti-TNF-alpha therapy (Beneficial effects have been noted with both infliximab, particularly for ocular disease, and etanercept, particularly for mucosal and skin manifestations)
- Interferon alpha (Review articles have shown good response in mucocutaneous, and ocular disease)
In summary, “Behcet’s Disease: What It Is and Isn’t” was an enlightening lecture that conveyed Behcet’s as a syndrome of innumerable signs and symptoms tied together with the common thread of recurrent painful aphthous ulcers, painless genital ulcers, uveitis and the pathergy reaction. It is a syndrome with a spectrum of severity and the result of the interplay of genes and environmental exposure. What Behcet’s is not is an easily diagnosed entity with obvious treatment guidelines. It is not clearly an autoimmune disorder with readily assayed antibodies nor is it a straightforward radiological diagnosis. Behcet’s is a clinical diagnosis made by the astute physician, and most appropriately treated by a Rheumatologist well-versed in current, evidence-based practice.