Behcet’s Disease. A Case Report

Abstract

Behcet's disease is a rare autoimmune systemic vasculitis. It usually presents with a symptom complex involving primarily mucocutaneous lesions, genital lesions, and uveitis. When it involves the lower extremity, venous and arterial disease predominates, and joint involvement occurs in approximately 50% of patients. We present a patient with Behcet's disease who was initially referred to us for chronic toenail pathology.

Behcet's disease was first reported by Huluci Behcet in 1937, who described a complex of orogenital apthosis, hypopyon, and iritis.[1] It remains a clinical diagnosis, with the most common systemic manifestations being oral and genital ulcerations, cutaneous skin lesions, and uveitis.[2] Historically, Behcet's disease manifestations in the lower extremity have been described as primarily venous claudication, possible ulcerations, and cutaneous lesions.[1] Behcet's disease is a rare systemic vasculitic disorder with recurrent attacks of acute inflammation involving all sizes and types of vessels, with veins more commonly affected than arteries.[3] The inflammation is often self-limiting, and relapsing episodes are a hallmark of the disease.[2] The usual onset is in the third decade of life, with males being more severely affected than females.[3] It is associated with significant morbidity and premature mortality. Unfortunately, the etiology of Behcet's disease is unknown and there is no known cure.[2] However, HLA-B51 has been associated with Behcet's disease, and the herpesviruses have been thought to provoke the onset with increased seroprevalence.[4] There are no pathognomonic signs or laboratory, radiologic, or histologic findings in the disorder.[4] Disease criteria include three incidences of oral ulcers within 1 year plus two of the following: recurring genital ulcers, eye inflammation, characteristic skin lesions, or a positive pathergy test.[1]

The most common manifestations of Behcet's disease are oral and genital ulcerations, cutaneous skin lesions, and uveitis.[2] The most common ocular manifestation is bilateral panuveitis associated with retinal vasculitis. Other severe manifestations that are less frequent include involvement of the central nervous system including neuropathy, the main large vessels, the musculoskeletal system, the renal system, and the gastrointestinal tract.[2] Cutaneous lesions involved often present as papules that can form ulcerations that are difficult to heal, which are common in the lower extremity.[5] A study by Fei et al[6] analyzed the prevalence of vascular involvement in Behcet's disease. They found that 12.8% of patients had vascular involvement and that venous disease (70.6%) was more common than arterial disease (54.9%). The most frequent arterial lesions were in the aorta, lower extremity, and pulmonary arteries. Superficial thrombophlebitis can cause overlying erythema that may be confused with erythema nodosum.[6] Heart involvement, which ranges from 7% to 46%, includes endocarditis, myocarditis, pericarditis, intracardiac thrombosis, endomyocardial fibrosis, myocardial aneurysm, and valve diseases.[7] Muscular involvement is rare, especially in adults.[8] Neurologic involvement can include headache, diplopia, and pyramidal syndrome.[4] Fatemi et al[9] described 51% joint involvement in patients with Behcet's disease, with the most frequent pattern being monoarthritis. Many patients also exhibit suicidal ideation due to the potential severity of the disease and the lack of a cure.[4]

In the lower extremity, the most frequent finding is venous claudication with frequent deep venous thrombosis, which can be followed by vena cava thrombosis and various arterial aneurysms.[3,4] Patients can experience substantial pain in their skeletal system, including the feet and ankles.[4]

The main treatment is symptomatic and involves immunosuppressants such as anti–tumor necrosis factor agents and cytokine inhibitors.[4] Ocular manifestations are treated with oral corticosteroids.[4] Colchicine is used to treat relapsing mucocutaneuous lesions or to prevent their occurrence.[10] Vascular involvement may be treated with anticoagulation therapy. In patients treated with immunosuppressants alone compared with immunosuppressants and anticoagulation therapy, the vascular relapse rate was similar (29% and 22%, respectively).[11] Oral ulcerations have been treated with the phosphodiesterase inhibitor apremilast.

Case Report

A 32-year-old man was referred to Des Moines University, Des Moines, Iowa, for chronic pain, bleeding, and erythema of his toenail beds for the past year. The patient also related generalized pain in both feet. All ten toenails had been permanently removed via a phenol and alcohol technique within the past year owing to toenail pain. He had previously been evaluated at an academic medical center for his current toenail condition and foot pain, but no diagnosis was provided. Management from the previous institution consisted of only a tapering dose of oral corticosteroids, which did not provide relief. The patient related a history of cold exposure several years previously that caused mild frostbite to the face, fingers, and toes. Attempts at conservative management included periodic meloxicam at a dosage of 15 mg/d, which provided partial alleviation of his toe pain, and custom-made orthoses, which relieved his generalized foot pain, but the toe discomfort remained. He was unable to work due to the severe pain.

The patient denied any current medical conditions or illnesses; allergies to drugs, food, or the environment; and no other prescription or over-the-counter medications besides meloxicam. Within the past year, he had bilateral vein ablation surgery for chronic leg edema, which the patient related as being caused by incompetent valves. He used chewing tobacco daily. He related that both his parents were alive and well without any contributing medical problems.

His review of symptoms was remarkable for generalized fatigue and a long-term history of oral mucosal and sublingual lesions that occurred once or twice a month that were determined to be secondary to stress. He related quarterly eruptions of skin lesions to his face, arms, and legs that were diagnosed as impetigo and treated with oral clindamycin. The lesions would clear within 2 weeks of starting clindamycin therapy. He denied any eye problems, chronic back pain, generalized myalgias or arthralgias, chronic diarrhea or constipation, previous sexually transmitted diseases, chronic urinary tract infections, or depression.

Physical examination revealed an anxious individual with palpable pedal pulses within normal limits and an increased bilateral hallux capillary refill time of greater than 5 sec. The toes were cold to the touch, with a ruborous-cyanotic hue. There was no edema present to the foot or toes. There were small eschars present on a few toenail beds with minimal nail plate remnants. The musculoskeletal examination was unremarkable except for a bilateral flexible flatfoot deformity. There were no active oral or skin lesions present on visual examination.

A preliminary diagnosis of undifferentiated connective tissue disease was made based on the symptom cluster of possible Raynaud's disease, phlebitis, vasculitis, and foot arthralgia. Laboratory screening results were positive only for a slightly elevated C-reactive protein level (0.6 mg/dL [reference range, 0–0.5 mg/dL]) and erythrocyte sedimentation rate (23 mL/hr [reference range, 0–15 mL/hr]). Complete blood cell count, antinuclear antibody, rheumatoid factor, and HLA-B27 were all negative. The patient was then referred for a rheumatology consult.

When presenting to a rheumatologist 6 weeks later, oral lesions were discovered, and the patient reported blurry vision during the past 9 years with recent acute vision loss in his left eye. He also related periodic genital ulcers. Laboratory evaluation showed a vitamin D₃ deficiency of 24 ng/mL (reference range, 30–100 ng/mL), elevated histone antibodies of 1.8 U (reference range, <0.9 U), thyroid peroxidase antibodies of 286.1 IU/mL (reference range, <9.0 IU/mL), and a C-reactive protein level of 1.6 mg/dL (reference range, <1.0 mg/dL). All other test results were negative. The patient was provisionally diagnosed as having Behcet's disease and was started on colchicine at 0.6 mg twice daily and vitamin D₃ at 10,000 IU weekly by mouth. The patient was also referred to the ophthalmology department. A chorioretinal scar, retinal edema, and retinal phlebitis were discovered in his left eye. Results of further laboratory testing performed by the ophthalmology department were negative for antineutrophilic cytoplasmic antibodies, nontreponemal antibodies, serum lysozyme (to evaluate possible sarcoidosis), and lyme antibodies. In addition, the patient had normal levels of angiotensin-converting enzyme (to evaluate possible sarcoidosis).

At his initial follow-up with the rheumatology department, the patient reported a decrease in his oral lesions but had continued pain in his feet and hands. He was administered 120 mg of methylprednisolone acetate (Depo-Medrol; Pfizer Inc, New York, New York) intramuscularly for immediate pain relief. He was prescribed azathioprine, 175 mg/d, and adalimumab (Humira; AbbVie Inc, North Chicago, Illinois), 40 mg subcutaneously every other week. He was also to continue taking colchicine at 0.6 mg twice daily. Free thyroxine and thyrotropin tests were ordered. The patient was lost to follow-up at this point.

Discussion

We presented a case of Behcet's disease that displayed lower-extremity symptoms in a 32-year-old-man. Unfortunately, there was a substantial delay in diagnosis for several years, with signs and symptoms attributed to unlikely etiologies considering the nature of the concerns and the age of the patient. The patient's oral cavity ulcers were determined to be caused by stress. Recurrent aphthous stomatitis is the most common ulcerative disorder affecting the oral cavity.[12] Although stress has been emphasized as a cause of the stomatitis, onset of the lesions seems to peak between ages 10 and 19 years.[12] If the ulcers continue to occur or increase in severity after the third decade of life, it should alert one to search for a medical condition as the underlying cause, such as an immunologic disorder or Behcet's syndrome.[12] His skin lesions were diagnosed as impetigo, which resolved 2 weeks after a course of oral clindamycin therapy. Although impetigo can occur in adults, it is much more common in children aged 2 to 5 years, and either the bullous or nonbullous form will resolve without treatment within a few weeks.[13] The toenail pathology was most likely caused by chronic small-vessel vasculitis, which led to the abnormal shape and discomfort and periodic nail bed hemorrhage after nail removal. Chronic venous insufficiency in his age group is extremely uncommon. In a prevalence study in Scotland, venous insufficiency was not found in males younger than 34 years,[14] prompting one to consider other etiologies for his edema, of which Behcet's disease is a possibility. The extent and severity of his toe, foot, and ankle pain, combined with his other pertinent review-of-system findings, strongly suggests some type of inflammatory arthropathy. As previously detailed in this case report, Behcet's disease is a disorder without pathognomic laboratory test or radiologic findings, and as such the medical history becomes the chief tool to aid in its diagnosis. Behcet's disease should be considered in a differential diagnosis when associated with venous disease, mucocutaneous lesions, and joint pain in the lower extremity.

Financial Disclosure: None reported.

Conflict of Interest: None reported