Painful oral ulcers leave teen speechless

This adolescent had several deep, painful, sharply demarcated ulcers involving the lip and buccal mucosa.

The Case

A 17-year-old white female is transferred from an outside hospital with the chief complaint being painful oral ulcers. Over the last 72 hours, the pain from her ulcers has progressively worsened, leading to the inability to speak or eat. She also has a diffuse papulopustular rash. There is an extensive family history of autoimmune disease, and she tested positive for mononucleosis 2 months prior to hospitalization.

Diagnosis: Behçet syndrome

Behçet syndrome is a systemic vasculitis affecting both small and large vessels of the venous and arterial systems, characterized by relapsing episodes of inflammation.^1-3 It can affect virtually all body systems.

Epidemiology

Behçet syndrome occurs most commonly among Asian and Eurasian populations and slightly more among men than women.¹ The disease usually develops between the ages of 20 to 39 years, and rarely before puberty or after 50 years of age. The incidence in the United States and Northern Europe is 0.12 to 0.64 per 100,000 and may vary by ethnicity.

History and pathogenesis

Behçet syndrome is named after Hulusi Behçet (1889-1948), the Turkish dermatologist who first recognized the syndrome in one of his patients in 1924 and reported his research on the disease in the Journal of Skin and Venereal Diseases in 1937.⁴ Symptoms of this disease may have been described by Hippocrates several centuries BC.⁵

The cause of Behçet syndrome is unknown, but it is thought to involve an autoimmune process triggered by an infectious or environmental agent in a genetically predisposed individual. There is a potential association with human leukocyte antigen HLA-B51.^1-3

Presentation and diagnosis

The earliest sign of Behçet syndrome is often recurrent aphthous ulcers.⁶ Genital ulcers occur in 57% to 93% of patients; ocular disease in 29% to 100% of patients; and skin findings in 38% to 99% of patients. Oral ulcers are often presenting symptoms in children aged younger than 6 years. The disease in childhood is similar to adult disease except for more frequent perianal aphthosis and arthralgia; less frequent genital ulcers; and more severe uveitis.

Behçet syndrome is a clinical diagnosis. There are several published diagnostic criteria, including the International Study Group criteria.⁷

The characteristic painful oral ulcers that often are the first presentation of Behçet syndrome initiate an extensive workup including, but not limited to, herpetic stomatitis, herpes zoster, mononucleosis, coxsackievirus, Sweet syndrome, leukemia, pemphigus, pemphigoid, lichen planus, recurrent multiforme, and cyclic neutropenia.^8,9 It is especially important to rule out Epstein-Barr virus, cytomegalovirus, primary syphilis, and human immunodeficiency virus in adolescents with genital ulcers.

Treatment

It is important to consider the patient’s age and gender, extent and severity of disease, and the most affected organs when tailoring therapy. For oral and genital ulcers, utilize topical relief, including lidocaine (Xylocaine) and/or sucralfate (Carafate). Cyclosporine (Sandimmune, Neoral, Gengraf) can be used during active lesions, and colchicine (Colcrys) may prevent oral and genital ulcers as well as treat arthritis. For ocular lesions, azathioprine (Azasan) and systemic steroids can be used, and cyclosporine or infliximab (Remicade) may be used for more severe lesions. There is limited evidence for treating other systemic manifestations.^1,10

Our patient

Given that Behçet syndrome is a clinical diagnosis that can resemble many infectious disease processes, our patient’s initial evaluation began with a focus on common viral etiologies such as herpes and coxsackievirus. After minimal improvement and a prolonged course despite antivirals, oral biopsies were performed. Finally, with rheumatologic disease in the differential, an ophthalmologic exam was performed that confirmed retinal vasculitis. The diagnosis of Behçet was made given the oral lesions and ophthalmologic findings. Our patient did not have genital ulcers at any time during her hospitalization. She was started on intravenous steroids and she rapidly improved. Azathioprine was started shortly after discharge and she is now doing well, according to her pediatric rheumatologist.

Prognosis

The disease course may vary depending on ethnic, geographic, and individual differences (more severe in Eastern and Mediterranean regions; men; and younger individuals).¹ Behçet syndrome involves a variable course with relapses and remissions, but over time many patients achieve complete remission. Blindness can occur with repeated eye inflammatory attacks. Death, which rarely occurs, is most likely caused by thrombosis or aneurysm.^1,8

REFERENCES

1. Mendes D, Correia M, Barbedo M, et al. Behçet's disease-a contemporary review. J Autoimmun. 2009;32(3-4):178-188.

2. Yazici Y, Yurdakul S, Yazici H. Behçet's syndrome. Curr Rheumatol Rep. 2010;12(6):429-435.

3. Suzuki Kurokawa M, Suzuki N. Behcet's disease. Clin Exp Med. 2004;4(1):10-20.

4. Behçet H. Über rezidivierende, aphtöse, durch ein Virus verursachte Geschwüre am Mund, am Auge und an den Genitalien. Dermatol Wochenschr. 1937:36:1152-1157.

5. Johns Hopkins Vasculitis Center. Behcet’s disease. Available at: http://www.hopkinsvasculitis.org/types-vasculitis/behcets-disease/. Accessed March 12, 2014.

6. Zouboulis CC. Epidemiology of Adamantiades-Behçet's disease. Ann Med Interne (Paris). 1999;150(6):488-498.

7. Criteria for diagnosis of Behçet's disease. International Study Group for Behçet's disease.  Lancet. 1990;335(8697):1078-1080.

8. Riera Matute G, Riera Alonso E. Recurrent aphthous stomatitis in rheumatology. Reumatol Clin. 2011;7(5):323-328.

9. Woo SB, Stone JH, Kraft S. Case records of the Massachusetts General Hospital: Case 22-2013: a 51-year-old woman with epistaxis and oral mucosal ulcers. N Engl J Med. 2013;369(3):265-274.

10. Yurdakul S, Yazici H. Behçet's syndrome. Best Pract Res Clin Rheumatol. 2008;22(5):793-809.

Mr Pulcini is a fourth-year medical student at Tufts University School of Medicine, Boston, Massachusetts. Dr Garg is pediatric hospitalist and director, Pediatric Residency Program, Floating Hospital for Children at Tufts Medical Center, Boston. Dr Cohen, section editor for Dermcase, is professor of pediatrics and dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland. The authors and section editor have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Vignettes are based on real cases that have been modified to allow the authors and editor to focus on key teaching points. Images also may be edited or substituted for teaching purposes.