Isolated brachial artery aneurysm: a rare presentation of paediatric Behçet’s disease

Abstract

Behçet’s disease is a rare disease characterised by recurrent oral ulcers, with systemic manifestations including genital ulcers, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease and arthritis. Most clinical manifestations of Behçet’s disease are believed to be due to vasculitis. The heterogeneous clinical spectrum is influenced by sex, ethnicity and country of residence. Vascular manifestation in the form of isolated large brachial artery aneurysm is rare in children. Treatment involves aneurysmorrhaphy to avoid rupture or ischaemic sequelae in addition to lifelong medical management to control vasculitis.

Background

Behçet’s disease is a rare disease characterised by recurrent oral ulcers with systemic manifestations including genital ulcers, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease and arthritis. Onset is insidious. The disease is usually seen in young adulthood with a peak age of onset of 25–30 years, but it is also occasionally seen in children before the age of 16 years in 4–26% of cases.¹ Paediatric onset is very rare and carries a strong genetic component. The clinical spectrum of Behçet’s disease is heterogeneous and is influenced by sex, ethnicity and country of residence.

Behçet’s disease is an autoinflammatory disease with recurrent and self-limiting attacks. Vascular complications (vasculo-Behçet’s disease – a variable vessel vasculitis) severely affect the course of the disease and are seen in 1.8–21% of children.² The veins are most commonly affected, resulting in either superficial thrombophlebitis or deep vein thrombosis. Arterial involvement is seen in 3–12% of patients.² The most common manifestation is pulmonary artery aneurysm, which is an important cause of morbidity and mortality. Peripheral artery aneurysms are rarely seen in children. Most reports involve adult-onset vasculo-Behçet’s disease. We present the case of a two-year-old child who presented with an isolated brachial artery aneurysm and was detected to have positive HLA B51 antigen.

Case history

A two-year-old male child presented to the vascular clinic with a history of swelling in the right upper arm for one month. He had no prior history of trauma, nor had there been central or umbilical line placement. The child had uneventful perinatal history. He had been born at full term in a normal delivery with smooth transition. On physical examination, a pulsatile swelling was noticed in the distal part of the right arm which measured 5×4cm. The overlying skin was normal, firm in consistency and tender with palpable distal pulses in the forearm.

The child had no obvious dysmorphism except for the mild hyperextensibility of thumbs. His systemic examination was unremarkable. A duplex scan showed 5×4.5cm fusiform aneurysm arising from the distal brachial artery, with an echogenic component noted in its lower aspect, suggestive of thrombus. Computed tomography angiography of the chest, upper limbs and abdomen revealed fusiform right distal brachial artery aneurysm measuring 5×4.5cm with partially layered thrombus. No other vascular pathology was detected (Figure 1A,B). Echocardiography revealed a normal heart. Urine microscopy, renal function test and ultrasound of the kidneys revealed that everything was within normal limits. Examination of the eye was normal. The child was positive for human leucocyte antigen (HLA B51) and antinuclear antibody. His C-reactive protein (CRP) level was 37.2 mg/l and erythrocyte sedimentation rate (ESR) was 52 mm/hour. Haemogram, liver function test and coagulation profile were within normal range.

Figure 1 .

(A, B) Computed tomography angiography of the right upper limb; three-dimensional reconstruction, showing fusiform aneurysm of distal right brachial artery. (C) Intraoperative image showing repair of the aneurysm with reverse saphenous vein graft harvested from the left leg.

The child was considered for repair of the aneurysm in view of its large size. Intraoperatively, a fusiform aneurysm measuring 5×4cm was noticed, which arose from the distal brachial artery, with a thrombus visualised on the anteromedial wall on opening of the aneurysm, with proximal and distal brachial artery clamped under 1 mg/kg systemic heparin. The aneurysm was repaired using a reverse saphenous vein graft harvested from the opposite lower limb (Figure 1C) and palpable pulse was confirmed intraoperatively.

The child had an uneventful postoperative period and he was discharged in a stable condition. Histopathology revealed vasculitis in the aneurysm wall (Figure 2). Diagnosis of Behçet’s disease was considered in view of the paediatric onset vascular disease (brachial artery aneurysm), HLA B51 positivity and vasculitis in the histopathology of aneurysm wall. He was started postoperatively on medical management with syrup prednisolone 1 mg/kg (10 mg) for four weeks, gradually tapered over four weeks, and kept on maintenance dose of 2.5mg for six weeks, to avoid any remission. His elevated ESR and CRP levels normalised within one month with value of 12mm/hour and 5mg/l, respectively. He is currently doing well, without being on steroids at six months of follow-up. There is good distal perfusion of the right upper limb. He is on six-monthly follow-up with regular surveillance of vasculitis inflammatory markers (ESR and CRP), clinical assessment of the repaired aneurysm site (to look for any thrombosis/aneurysm degeneration of vein) and to detect any new development of symptoms or signs of Behçet’s disease.

Figure 2 .

Histopathology of the arterial wall showing: (A) thickened intima (I) with intense hyalinisation of media (M) and adventitia (A), 100 × magnification; (B) Masson’s trichrome stain highlighting the collagen fibres as blue in media and adventitia, 100 × magnification. (C) The intima shows proliferation with infiltration by lymphocytes, plasma cells and scattered neutrophils, and areas of myxoid change causing destruction of the internal elastic lamina, 400 × magnification. (D) Adventitia showing vasa vasorum (v) being infiltrated by neutrophils and lymphocytes, 400 × magnification.

Discussion

Behçet’s disease was first described by the Turkish dermatologist Hulusi Behçet. The disease has a peculiar epidemiological distribution, having a high prevalence among communities around the old ‘Silk Road’, a wide area between the Mediterranean countries and eastern Asia.³ The higher prevalence of Behçet’s disease is demonstrated in Turkey and Northern Jordan, and it is also seen in Korea, Northern China, Iran and Israel. Outside this geographical area, cases have been reported from all over the world due to better understanding and increasing awareness of this disease. The prevalence of this disease is reported to be 10.3/100,000 globally, 119/100000 for Turkey, 31.8/100000 for the Middle East, 4.5/100000 for Asia, 3.3/100000 for Europe and 3.8/100000 for North America.¹

The aetiology of Behçet’s disease is believed to be a complex interaction between genetic and environmental factors. Vascular involvement in Behçet’s disease can affect vessels of any size and type, and has been recently classified as variable vasculitis.⁴ Paediatric patients generally have few symptoms and time of diagnosis is usually between three and five years. The main pathological feature is inflammation of the vessel wall leading to thrombus formation or aneurysmal degeneration, which may lead to rupture and embolism. Diagnosis of paediatric Behçet’s disease is difficult because of its rarity in childhood and the lack of validated diagnostic criteria obtained from adult studies. A study of paediatric Behçet’s disease has defined the criteria for paediatric patients (Table 1). Presence of three or more of the six criteria is required for a diagnosis.⁵

Table 1 .

Paediatric criteria for Behçet’s disease

Criteria	Expression
Recurrent oral ulcers	At least three attacks/year
Genital ulceration	Typically, with scar
Skin involvement	Erythema, necrotic folliculitis and acneiform lesion
Ocular involvement	Anterior uveitis, posterior uveitis, retinal vasculitis
Neurological	Except for isolated headaches
Vascular	Venous thrombosis, arterial thrombosis, arterial aneurysm

Behçet’s disease carries a strong genetic component and familial cases have been reported in 10–50% of patients.⁶ HLA B5 and, more specifically, its predominant suballele HLA B51 is strongly associated with Behçet’s disease. Affected males are the predominant carriers and they are associated with moderately higher prevalence of genital, ocular and skin manifestation and decreased prevalence of gastrointestinal manifestations. Besides HLA B51, which is the strongest risk factor, other suballeles (HLA A26, B15, B27 and B56) are independent risk factors for Behçet’s disease; HLA AO3 and HLA B49 are protective.⁷

In the present case, the child had a brachial artery aneurysm, positive status for HLA B51 and raised inflammatory markers (CRP and ESR), and histopathological examination of the resected specimen showed vasculitis. All these favoured a diagnosis of paediatric Behçet’s disease. However, in children, new symptoms appear with time. The distribution of clinical signs differs according to age, sex and ethnic background. The geographical variability of clinical symptoms is a prominent characteristic of this illness. The available paediatric Behçet’s disease cohort studies to date have shown that the age of onset of first symptom ranges between 7 and 11 years.⁸ The child in our case is two years of age, one of the earliest onsets of the Behçet’s disease reported. He will be under strict follow-up to avoid complications of other associated findings, which can evolve over the time in Behçet’s disease.

The large size of the brachial artery aneurysm mandated surgical intervention and the patient was successfully treated using the great saphenous vein, having a diameter of 2mm on preoperative ultrasonography, which was the same as that of the brachial artery. The disease-free saphenous vein was preferred for its better size match and patency compared with small diameter prosthetic graft. In the adult patient, for medium and large vessels, prosthetic grafts are preferred, as veins are susceptible to vasculitic changes.

Observational studies have shown that following surgical intervention, there is a role for medical therapy to prevent the recurrence of vasculitis, in the form of immunosuppression using cyclophosphamide and corticosteroids. We lack controlled trials to determine the optimal dose and duration of corticosteroids after surgical intervention. Further studies are warranted to address these controversial issues. Behçet’s disease is associated with recurrent attacks and an unpredictable course, which mandate surveillance for optimal treatment.

Conclusion

Vascular involvement in paediatric Behçet’s disease is rare and a brachial artery aneurysm is even rarer. The large size of the brachial artery aneurysm required surgical repair to avoid complications such as rupture, thrombosis and embolism. In children, Behçet’s disease often remains active, with new symptoms appearing over time, which makes surveillance mandatory.