What New Research on Behçet’s Tells Us About This Rare Disease

This article is dedicated to the many Behçet’s warriors we have lost since my diagnosis 20 years ago, in 2003. Your memory and impact in this life and with this illness will be remembered and revered forever.

May represents and serves as an opportunity to raise awareness about Behçet’s syndrome, an illness with which I have been fighting for at least 25 years.

Behçet’s syndrome (usually pronounced “BUH-shehts”) is a chronic and frequently systemic auto-inflammatory condition of unknown etiology. It is an unusual illness with diverse manifestations, often presenting very differently in different patients. Further, Behçet’s is a unique type of autoinflammatory vasculitis in that it affects all blood vessels of all sizes (i.e., both venous and arterial systems); since blood vessels are located everywhere in the body, Behçet’s can affect any part of the body.

Although there are recognized genetic factors that have associations with Behçet’s, namely the human leukocyte antigen (or HLA)-B51, which has been implicated as the antigen with the most significant correlation with Behçet’s — candidate association studies have shown that HLA-B51 was actually carried in 60% of Behçet’s patients — not all people who carry noted genetic factors present with Behçet’s. The exact cause of Behçet’s is currently unknown, although it is frequently thought that a virus or bacterium may trigger the illness in those with and without genetic predispositions. With an unknown etiology as well as three currently recognized phenotypes, Behçet’s, which is often called a “disease” is technically a “syndrome.”

The three main phenotypes now recognized to exist within Behçet’s syndrome are 1. the mucocutaneous and articular phenotype (cases that present with various ulcerations and arthritis), 2. the extra-parenchymal neurological and peripheral vascular phenotype (cases that affect the central nervous system, or CNS, and include venous and arterial manifestations), and 3. the parenchymal neurological and ocular phenotype (cases that present with CNS involvement and eye disease; I implore the reader to research the difference in the terms “parenchymal” and “extra-parenchymal”!)

Intestinal disease, which closely resembles Crohn’s disease, often occurs in conjunction with these phenotypes of Behçet’s. Gastrointestinal (GI) symptoms can include bleeding ulcers anywhere in the GI tract, gastoparesis, as well as nausea, vomiting, diarrhea, and treatment-resistant constipation. Patients can — and often do — present with overlapping phenotypes, such as having ulcerations, arthritis, and eye involvement; treatment is aimed at the most serious and aggressive presenting symptom. Since there are no tests that can either confirm or exclude a diagnosis of “Behçet’s Syndrome,” the diagnosis must be made based on clinical findings.

The most common defining clinical manifestation of Behçet’s is the presence of frequently recurrent and painful mouth ulcers, which present in nearly all cases — an estimated 98% of those with confirmed Behçet’s have oral ulcers. The 2% of those without mouth lesions represent those who are diagnosed cases that present with other clinical manifestations but do not include oral ulcerations.

Behçet’s usually presents in individuals between the approximate ages of 20-40. Unlike many other rare diseases, there is a vast difference in case presentation based on geography and ethnicity; Behçet’s syndrome is also sometimes referred to as the “Silk Road Disease” because prevalence of the syndrome along the current geographical stretches of Northern Africa and the Middle East across and into East Asia, known as the “Silk Road” for the ancient trading ports that once defined these areas, remain the highest in the world. For example, disease prevalence in Turkey, widely recognized as having the highest Behçet’s prevalence in the world, is estimated to be as high as 300-400 cases per 100,000 (100 times more prevalent than Behçet’s is in much of Northern Europe); Behçet’s remains one of the leading causes of blindness of men in Japan. There is a Japanese drama series,「愛し君へ」,“To the One I Love”, from 2004 about a patient who goes blind from Behçet’s; some of the medicine presented is inaccurate, at best, but the series realistically portrays how this illness can affect individuals and speaks to how different ethnicities are affected by Behçet’s.

Eye disease, which is the hallmark of one of the three currently recognized phenotypes of Behçet’s occurs in about 50%-70% of patients. Ocular involvement often marks the point at which the illness is considered to have gone “systemic” and “severe;” manifestations include posterior uveitis, retinal vasculitis, and optic neuritis but can include surface inflammation and other very serious findings (the “cold hypopyon” is one such unique and fascinating finding that can occur with Behçet’s). Ocular involvement can lead to full or partial blindness in one or both eyes.

The other defining clinical features of Behçet’s listed above include painful genital ulcers that often last for weeks and tend to scar. Behçet’s also commonly presents with skin lesions that usually include but are not limited to pseudo-folliculitis, “acne-like” lesions, and erythema nodosum, typically on the lower extremities. In addition to these defining clinical features, arthritis that usually affects the medium-to-large joints on one side of the body (but can also affect any joints in the body) is often cited as a common presenting manifestation. These various lesions as well as arthritis constitute the first phenotype listed above. This phenotype seems to be the most common, the most easily treatable, and the type with the best long-term prognosis.

In addition to the aforementioned symptoms, two of the three Behçet’s phenotypes affect patients’ central nervous systems. CNS involvement is a significant cause of mortality in Behçet’s patients; manifestations can range from headaches to seizures to “brain fog” and “vacant episodes” to encephalitis of the brainstem and involvement of the midbrain and basal ganglia, cranial nerve palsies, and various lesions throughout the spinal cord and brain. Neurological and vascular manifestations are considered to be syndrome-defining. Vascular involvement, which can affect both veins and arteries, often affects veins more commonly than arteries (a further unusual feature of Behçet’s), and includes symptoms like deep vein thromboses, lesions of the cerebral venous sinuses and the superior and inferior vena cava, as well as pulmonary aneurisms which are a syndrome-specific clinical manifestation of Behçet’s. Due to chronic inflammation, constitutional manifestations including malaise, fatigue, and periodic fevers are also common presenting factors.

As mentioned above, treatment of Behçet’s generally aims at treating the most severe presenting symptoms. Since Behçet’s can be very difficult to treat, it is crucial for patients to be treated with medications aimed at their specific symptoms in a very aggressive manner. Treatments for Behçet’s range widely, from the utilization of fairly benign medications such as topical steroids and NSAIDs to more aggressive treatments for refractory illness like systemic steroids (and eye drops) as well as chemotherapeutic, immunosuppressive, and biologic agents (traditionally TNF-alpha inhibitors, although now many focus on more specific inflammatory interleukin pathways), and traditional DMARDs.

Behçet’s is considered a “rare disease” in the United States and the United Kingdom, with an approximate prevalence of 0.12 to 7.5 per 100,000 people. Behçet’s is an illness of flares and periods of lessened activity; it is estimated that after treatment for approximately 20 years, about half of Behçet’s patients will achieve remission. CNS and vascular involvement are still associated with high mortality rates. Behçet’s is a rare and unusual disease that is often resistant to treatment. Bringing much-needed awareness to Behçet’s is essential to saving lives, improving the lives of patients around the world, and achieving a higher rate of remission within a much faster time frame.

Research is always evolving, but for more information on Behçet’s syndrome, up-to-date research information, and even a physician finder, you can visit the Vasculitis Foundation. There is a foundation for Behçet’s in the U.S., the American Behçet’s Disease Association (ABDA). Other great resources include Behçet’s UK which is celebrating its 40th anniversary this year, Behçet’s Canada, rare disease websites like the National Organization for Rare Disorders (NORD) which is also celebrating it’s 40th anniversary this year, and sites that help connect patients who have been diagnosed with rare conditions like Behçet’s with other patients, like Rare Connect.

I hope you will celebrate Behçet’s Awareness Month with me by sharing articles like these, checking out the aforementioned resources, and perhaps even trying to connect with Behçet’s patients through social media — I can almost guarantee your kind gestures will be well received! If you are interested in showing your support by wearing a ribbon, the Behçet’s awareness color is blue. Thank you very much and I hope we can bring awareness to many more people and fight this insidious illness with information!