Lower limb hypertrophic osteoarthropathy can reveal aortic graft infection in Behcet syndrome

Sir, Pierre–Marie–Bamberger syndrome [1], or secondary hypertrophic osteoarthropathy (HOA), is characterized by clubbing of digits, periosteal new bone formation and synovial effusion. Secondary HOA accompanies a variety of disorders, thoracic affections in particular, and may precede clinical features of the disease. Forms of HOA localized to one or two limbs occur as the result of an endothelial injury, such as an infection of arterial aneurysms or vascular grafts [2]. We report the case of a 44-yr-old woman with Behçet disease (BD) with predominantly unilateral lower limb HOA revealing an aortic graft infection. The patient was diagnosed with BD because of recurrent episodes of oral and genital ulcers and pseudofolliculitis [3]. A pathergy test was negative. She also suffered from arthritis, three relapses of deep vein thrombosis despite continuous anticoagulation, and a history of an abdominal aortic aneurysm discovered at age 30. An aorto-biiliac graft and left femoral grafts had been inserted. She was hospitalized for fever, arthralgia and deep pain in the left leg. On examination, her temperature was 38°C and she had arthritis of the ankles and knees, and bilateral femoral murmurs. Eye and skin examinations were normal and there were no oral or genital ulcers. Biological tests failed to evidence infection. The level of C-reactive protein (CRP) in the blood was 40 mg/l. An abdominal computed tomography (CT) scan showed a 3-cm large right iliac aneurysm facing the proximal anastomosis of the left aorto-ilio-femoral graft. Bone X-rays revealed subperiostal new bone formation with corresponding hyperfixation on a bone 99Tc scintiscan (Fig. 1a and b). Treatment with corticosteroids, azathioprine and colchicine was rapidly efficient on general status, fever and arthralgia. Postero-anterior radiograph of both knees (a) shows periosteal apposition at the distal shaft of left femur and proximal shaft of left tibia, with a corresponding hyperfixation at 99Tc scintigraphy (b). (c) Scintigraphy with 67Ga-labelled leucocytes shows a retroperitoneal hyperfixation at the site of the proximal anastomosis of the aorto-iliac graft. (d) Reformatted sagittal images from a CT acquisition show a thickened and dense retroperitoneum around the graft and an air bubble close to the proximal anastomosis, highly suggestive of a perigraft infection. Two months later, she was readmitted for excruciating pain in the left lower limb associated with fever and severe anaemia. Blood cultures were positive for group D Streptococcus spp. and Escherichia coli. Scintigraphy with 67Ga-labelled leucocytes was highly positive on the vascular graft (Fig. 1c). Abdominal CT scan suggested a fistula between the aorta and the digestive tract (Fig. 1d). Surgery revealed a fistula between the D3 portion of the duodenum and the vascular graft close to the prosthetic fork. A bilateral axillo-femoral bypass graft was placed. Antibiotic treatment and surgery led to prolonged remission and improvement of the fixations on the bone 99Tc scintiscan. Since aortic graft infection has been described as a cause of secondary lower limb HOA, a growing number of cases of localized HOA revealing early cases of vascular graft infections have been reported [4]. In a review of 115 cases of HOA, deep infection was responsible for 2.6% of cases of periostitis. Patients usually suffer from progressive pain and swelling of one or both extremities, associated with radiographic periostosis; clubbing of the toes is rare [5, 6]. The pathogenesis of digital clubbing and HOA remains largely unknown. Current thinking suggests that localized activation of endothelial cells by an abnormal platelet population, with the ensuing release of fibroblast growth factors, plays a central role [2]. In the case of HOA associated with vascular infection, the substance that causes HOA could either be produced by vascular tissue or be a precursor activated by contact with abnormal vascular tissue. This theory is supported by the localization of HOA in the limb vascularized by the infected graft and clinical improvement after its removal [4, 5]. Diagnosis of HOA is made using physical examination and imaging studies, finding periostitis and ruling out osteonecrosis, although no international criteria exist [2]. Bone scintigraphy showing localized hyperfixation can help confirm the diagnosis. BD is characterized by recurrent oral and/or genital ulcers, uveitis, skin and joint involvement. Vascular manifestations appear in 9–38% of patients, mostly as vein thrombophlebitis. Arterial involvement including thrombosis, stenosis and/or aneurysms is less frequent (10–15% of vascular involvement) [7]. Aneurysms, sometimes described as arterial aphthae, may be multifocal and involve mostly the abdominal aorta and the pulmonary arteries. Vascular surgery entails a specific risk of recurrent aneurysm on the anastomosis, aortic–intestinal fistulas, graft infection and thrombosis. A combination of corticosteroids with immunosuppressive therapy is necessary to prevent relapse and appears to be more effective than corticosteroids alone [8]. In our patient, scintigraphy with radiolabelled leucocytes helped localize aorta infection, as in other cases [9]. The diagnostic yield of scintigraphy with radiolabelled leucocytes for aortic graft infections may not be as specific in BD as in other settings because specific vascular inflammation may occur without infection and thus enhance vascular fixation. Interestingly, high-dose steroids and azathioprine treatment did not appear to abate the HOA clinical features in our patient. The regression of HOA after treatment for graft infection is in favour of a causal link between vascular graft rejection and HOA, ruling out BD as a cause of HOA. Our observation points out the importance of early diagnosis of HOA, even if it affects the lower limbs or if digital clubbing is lacking, as it can permit early diagnosis of life-threatening vascular graft infection. Particular attention should be paid to patients with BD as they are prone to infectious complications, because of both arterial Behçet-specific inflammation and a long course of immunosuppressive therapy. The authors have declared no conflicts of interest. Internal Medicine Department, 1Radiology Department, 2Nuclear Medicine Department, 3Rheumatology Department, Bichat Hospital, Paris and 4Vascular Surgery Department, Beaujon Hospital, Clichy, France

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