BY NANA P. MATSUMOTO, & DEREK MEEKS, DO
A 16-year-old boy presented to a rural ED with a swollen jaw, painful blisters in the mouth, and earache for the past day. One week before, he had a fever with chills, sore throat, and dry coughs. He was not taking any medications, and his immunizations were up-to-date. He had a mild learning disorder but no significant past medical or surgical history.
An apthous ulcer, the most common and one of the earliest signs of Behçet's disease.
The patient's vital signs were within normal limits, and his physical examination revealed anterior cervical lymphadenopathy, sinus congestion, and small erythematous vesicles in bilateral tympanic membranes. There were vesicular clusters in the oral mucosa and a few shallow ulcers in the buccal mucosa and posterior pharynx. There was no evidence of facial edema, drooling, or airway compromise.
The patient was prescribed a narcotic pain reliever, and was discharged in stable condition with instructions to follow up promptly with dermatology to consider other diagnoses and treatments. Herpetic gingivostomatitis was suspected.
Two days later, the patient began having dysuria, followed by the appearance of genital lesions. He was admitted to the hospital where an evaluation by an infectious disease specialist revealed painful genital lesions in the urethra, similar lesions in the esophagus per endoscopy, and bilateral conjunctival injection. The patient was diagnosed with Behçet's disease, and was treated with colchicine.
Behçet's disease is an idiopathic chronic inflammatory disorder that was first identified in 1936 by the Turkish dermatologist Hulusi Behçet. Symptoms are multisystemic, with vasculitis underlying its pathophysiological characteristics. Presentation usually includes recurrent aphthous oral and genital ulcerations, arthritis, cutaneous and ocular lesions, and an exaggerated skin response to minor injury known as pathergy. Median age of presentation is 25 to 35 years old, and it is more common and severe in men. Other forms of clinical manifestations may be present in cardiac (pericarditis, endocarditis, myocarditis, venous and arterial occlusions), gastrointestinal (aphthous stomatitis), and neurological systems (aseptic meningitis, parenchymal lesions). (Arthritis Res Ther 2003;5:139.)
The etiology of Behçet's disease is unknown, although it is characterized as a genetically related, excessive T-cell-mediated inflammatory disorder involving veins and arteries. Studies have shown possible linkage of Behçet's disease to polymorphisms of genes HLA-B51, GIMAP, and IL12A. (Arthritis Rheum 2009;61:1287; Ann Rheum Dis 2013;72:1510.) Prevalence of Behçet's disease is recognized worldwide, but it is higher in Asian, Mediterranean, and Middle Eastern populations (80-370 per 100,000 in Turkey, 2-30 per 100,000 in Japan, Korea, Iran, Iraq, and Saudi Arabia), and is extremely rare in the United States (one per 100,000). (Ann Med Interne [Paris] 1999;150:488.) Delaying treatment may lead to long-term complications such as blindness, stroke, and vascular thrombosis.
No specific tests currently confirm the diagnosis. Instead it is based on clinical findings specified as the International Clinical Criteria for Behçet's disease. The patient should present with recurrent oral ulcerations (aphthous or herpetiform) at least three times in one year, plus any two of the following: recurrent genital ulcerations, eye lesions (uveitis or retinal vasculitis), skin lesions found in adult patients not being treated with corticosteroids (erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules), and a positive pathergy test read by a physician within 24-48 hours of testing. (Lancet 1990;335:1078.)
Severity of Behçet's disease varies from patient to patient, and treatment depends on the severity of the manifestations and organ systems involved, which can be minor or major. Much of the management is symptomatic and focuses on reducing discomfort and preventing serious complications. As with this patient, minor manifestations are those that interfere with the patient's quality of life but do not threaten any vital organ function, such as arthritis, oral aphthae, and genital and skin lesions. The recommended treatment is colchicine, while glucocorticoids and other immunosuppressives may be considered. Major manifestations are those with the risk of major organ damage, such as uveitis, encephalitis, and carditis, which require more specific treatment regimens. (Ann Rheum Dis 2008;67:1656.) Behçet's disease affects a multitude of systems, so it is common to have various specialists treating the affected area within their field of expertise. It is helpful to have a primary care physician or rheumatologist to coordinate the treatment and monitor the patient's progress.
Arytenoid cartilage ulcers (left) and the epiglottic ulcers (right) shown via endoscopy.
According to the Arab American Institute and U.S. Census, Middle Easterners ranked third among the fastest growing immigrant groups in the United States from 2010-2014, so physicians will be seeing an increased number of medical diseases unique to those populations if this trend in growth continues, particularly in urban areas where most live. The current prevalence of Behcet's disease in the United States is uncommon, but as at-risk populations increase, it would be prudent for clinicians to become more familiar with its presentation and treatment to avoid treatment delays and complications which may result in catastrophic patient outcomes.
Ms. Matsumoto is a medical student at Touro University of Nevada College of Osteopathic Medicine, where Dr. Meeks is an assistant professor, the chair of department of specialty medicine, and the director of clinical systems.