Multiple Ulcers in a Middle-Aged Female
A 58-year-old white female presents to the family physician as a new patient. Her chief complaint is fatigue and anemia. She endorses multiple negative work-ups including negative chest film, colonoscopy, EGD, and marrow studies.
There has been a 50 lb weight loss in the past year, which she attributes to loss of appetite and constipation. She denies fever, chills, night sweats, or shortness of breath. She has noticed worsening vision and multiple, recurring mouth ulcers. She remarks that blisters occur every time she nicks her hands while working at a local hardware store and they slowly resolve over 1-2 weeks. She also complains of genital ulcers but denies any sexual contact for over 2 years.
Her medical history includes multiple courses of antibiotics for presumed skin abscesses, a toe amputation secondary to infarction, and a recent negative screening mammogram. She recently quit smoking.
Physical examination. Physical exam reveals a tired-appearing, middle age female. Oral exam reveals poor dentition and several oral aphthous ulcers (Figure 1). There are multiple flat, hyperpigmented lesions and scares lining the forearms from a history of “abscesses and blisters” (Figure 2 and 3).
Diagnosis. Behçet's disease is a multisystem disorder driven by an underlying vasculitis, which occurs in arteries and veins of all sizes.1 It is a clinical diagnosis based on exam findings. The International Study Group Criteria for Diagnosis (ISG) established the most widely agreed upon clinical criteria for defining Behçet's in 1990. They include recurrent oral ulcerations at least 3 times in 1 year, plus 2 of the following: recurrent genital ulcers, uveitis, or retinal vasculitis, skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules), and/or a positive pathergy test.2 These criteria may exclude individuals who would otherwise benefit from treatment of milder forms of Behçet's and thus other diagnostic criteria exist but are beyond the scope of this case report.3
Clinical manifestations. The above criteria represent the most common clinical findings in Behçet's with oral aphthous ulcers being the most common and usually first presenting sign. However, involvement of virtually every organ system has been demonstrated. Painful ulcers can affect the genitalia, occurring on the glans, scrotum, or labia. Ocular involvement is the chief cause of morbidity with findings including anterior and/or posterior uveitis, pain, blurry vision, light sensitivity, tearing, or injection.4 Pathergy is a hypersensitivity skin reaction to pin prick, which results in a local pustule formation. It has been seen less since the onset of disposable needles, but is considered unique to Behçet's. Pathergy is typically only seen during active disease but may be the only clinical finding or not seen at all in milder forms.1,5 Other findings include deep vein thrombosis, superficial thrombophlebitis, vaso-occlusive disease, polyarthritis, gastrointestinal ulcerations, and inflammation mimicking inflammatory bowel disease/syndrome.4,6 Central nervous system (CNS) involvement has also been documented to include aseptic meningoencephalitis, headaches, confusion, stroke, dementia, and personality change.7
Etiology. Originally thought to be a variation of syphilis, the etiology of Behçet's is not fully understood but it likely involves a genetic predisposition in association with autoimmune, environmental, or infectious factors. No clear Mendelian pattern of genetics has been established but multiple gene expression has been attributed to the disease, including HLA-B51.8
Epidemiology. Classically, this illness affects 20 to 40-year-olds of Middle Eastern and Asian descent.4 Prevalence is much lower in Western countries, but is estimated at about 5.2 in 100,000 in North America.9
Treatment. Our patient found immediate relief of symptoms and improvement in quality of life with the administration of oral corticosteroids, the mainstay of Behçet's treatment.10 However, there are many other treatment modalities being studied. Many have found success in anti-TNF agents including infliximab and etanercept.5,10 T-cell suppression with azathioprine has shown benefit in some studies.11 Mixed results are also seen with colchicine and cyclophosphamide therapy.12,13 At the time of this report, our patient was being managed with azathioprine and colchicine but had noticed a recurrence of aphthous ulcers as her oral steroids were tapered down.
Prognosis. Patient outcomes largely depend on the variation and severity of disease. The illness typically waxes and wanes over many decades with death usually occurring as a result from ocular, CNS, and vascular disease.4
- Chang H, Cheon K. The clinical significance of a pathergy reaction in patients with Behçet's disease. J Korean Med Sci. 2002;17:371-374.
- Tunç R, Uluhan A, Melikoğlu M, et al. A reassessment of the International Study Group criteria for the diagnosis (classification) of Behçet's syndrome. Clin Exp Rheumatol. 2001;19 (Suppl 24):S45-S47.
- Lee S. Diagnostic criteria of Behçet's disease; problems and suggestions. Yonsei Medical Journal. 1997;38(6): 365-369
- Gurler A, Boyvat A, Tursen U. Clinical manifestations of Behçet's disease: an analysis of 2147 patients. Yonsei Med J. 1997;38(6):423-427.
- Sfikakis P. Behçet's disease: a target for anti-tumour necrosis factor treatment. Ann Rheum Dis. 2002;61(Suppl II):ii51-ii53.
- Houman M, Ghorbel I, Ben Salah I, et al. Deep vein thrombosis in Behçet's disease. Clin Exper Rheumatol. 2001;19(Suppl 24):S48-S50.
- Araji A, Shariquie K, Al-Rawi Z. Prevalence and patterns of neurological involvement in Behcet's disease: a prospective study from Iraq. J Neural Neurosurg Psychiatry. 2003;74:608-613.
- Verity D, Wallace G, Vaughan R, et al. Behçet’s disease: from Hippocrates to the third millennium. Br J Ophthalmol. 2003;87:1175-1183.
- Calamia K, Wilson F, Icen M, et al. Epidemiology and clinical characteristics of Behçet's disease in the US: a population-based study. Arthritis Rheum. 2009;61(5):600-604.
- Pipitone N, Olivieri I, Cantini F, et al. New approaches in the treatment of Adamantiades-Behçet's disease. Curr Opin Rheumatol. 2006;18(1):3-9.
- Yazici H, Pazarli H, Barnes C, et al. A controlled trial of azathioprine in Behçet's Syndrome. N Eng J Med. 1990;322(5):281-285.
- Yurdakul S, Mat C, Tüzün Y, et al. A double-blind trial of colchicine in Behçet's syndrome. Arthritis Rheum. 2001;44(11):2686-2692.
- Ozyazgan Y, Yurdakul S, Yazici H, et al. Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet's syndrome: a single masked trial. Br J Ophthalmol. 1992;76(4):241-243.