True Case

and false aneurysms in Beh et's disease: report with ultrastructural observations

A n t o n i o Freyrie, M D , Oreste Paragona, MD , Giovanna Cenacchi , M D , Gianandrea Pasquinelli , MD, Germana Guiducci , BSc, and Gian Luca Faggiol i , MD, Bologna, Italy

One o f the most important aspects of Beh~et's disease is aneurysmal arteriopathy. The major problem of this complication is its tendency to develop recurrent false aneurysms at anastomotic and traumatic sites, such as angiographic punctures. We present a clinical case in which five aneurysms, some true, some false, were operated on during a period of 6 years, with the aid of ultrastructural observations o f the wall o f a true and a false aneurysm. One of the true aneurysms, localized in the aorta, was treated by direct aneurysmorraphy, and the 6-year follow-up demonstrated the absence o f recurrences. Based on both this experience and the data in the literature, we suggest that the most appropriate surgical approach would, when possible, be direct aneurysmorrhaphy. (J VASC SURG 1993;17:762-7.)

In 1937 Behqet 1 described a new disease that subsequently took his name, characterized by a triad o f symptoms: uveitis and oral and genital ulcers. In 1961 Mishima et al.2 reported an abdominal aortic aneurysm in a patient with Beh~et's disease. In 1979 Kingston et al.3 described an inguinal aneurysm at the site o f a previous angiographic puncture in a patient with Beh~et's disease. In 1988 Barlett et al. 4 reported a clinical case in which there were 14 aneurysms, some anastomotic.

The presence o f an inflammatory type (most likely on an autoimmune basis) obstructive or dilatational disease o f medium- and large-size arteries has an incidence o f 8% in Behqet's diseasefi In addition to the fact that this complication represents the most common cause of death in patients with Beh~et's disease, 4 it creates a complex technical problem for the surgeon. We therefore report a clinical case, significant for its aneurysmal complications, with the support o f ultrastructural morphologic data.

CASE REPORT

The patient is a 36-year-old white man from southern Italy, with no family history of Beh~et's disease.

From the Department of Vascular Surgery (Drs. Freyrie, Parag- ona, and Faggioli) and the Institute of Clinical Electron Microscopy (Drs. Cenacchi, Pasquinelli, and Guiducci), Uni- versity of Bologna.

Reprint requests: Antonio Freyrie, MD, Cattedra di Chirurgia Vascolare, Universitfi di Bologna, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.

Copyright © 1993 by The Society for Vascular Surgery and International Society for Cardiovascular Surgery, North Amer- ican Chapter.

0741-5214/93/$1.00 + .10 24/4/39752

762

In March 1984, at the age of 29 years, he reported an episode of tight leg thrombophlebitis with fever, nodular inflammatory formations in the lower limbs, and myar- thralgia. Two months later a scrotal ulcer appeared that recurred twice in the following years. In December 1984, a fast-enlarging pulsating mass was noted in the left groin. The patient was submitted to surgery in another institution with resection of the femoral aneurysm with an iliac-to- common-femoral-artery Dacron bypass. Six months later a fast-enlarging false aneurysm appeared at the site of t ~'~'~ previous operation, and in the same institution a new bypass was performed from the iliac artery to the superficial femoral artery with ligation of the deep femoral artery and removal of the old graft. During this period, the patient recalls the appearance of oral aphthae. After an additional period of 6 months (December 1985), the patient was referred to our institution with suspected graft infection caused by the presence of a painfifl inguinal mass, confirmed by computed tomographic scan, with skin inflammation and fever. An axillofemoral bypass with ringed polytetrafluoroethylene was performed. Four months later computed tomographic scanning and angi- ography showed a saccular aortic aneurysm (Fig. 1). The patient underwent aneurysmectomy with direct aortorrha- phy. This technique was performed because of the suspi, ~ cion that the aneurysm was mycotic; however, microbio: logic examination of the aneurysmal thrombus showed this to be negative. In the meantime the axillofemoral bypass occluded, but because of the good compensation it was decided not to treat it.

In January 1989 the oral aphthae and nodular erythema of the lower limbs reappeared together with the presence of chronic gastritis and dermatography. Beh~et's disease was diagnosed and medical therapy was started with colchicine, I mg/day. During the next 2 years, the scrotal and oral ulcers and the lower-limb phlebitis recurred but in a milder

JOURNAL OF VASCULAR SURGERY Volume 17, Number 4 Freyrie et aL 7 6 3

Fig. 1. Digital subtraction angiogram of infrarenal saccular aortic aneurysm.

form. In March 1991, at the age of 36 years, a small inguinal right mass with phlogosis appeared. This mass was found to have enlarged rapidly in July 1991; an- giography showed a pseudoaneurysm of the right com- mon femoral artery (Fig. 2), and the aneurysm was eKcised surgicaUy with polytetrafluoroethylene patching of ~ right ,common femoral artery. The cause of this aneurysm was probably the introduction of an angiog- raphy catheter 16 months earlier. This was the only known possible cause of this aneurysm, because trauma, intraarteria]i injections, or other surgical procedures had not been recorded at this level. The patient is currently under colchicine therapy, 1 nag/day.

Laboravory data included the following: human leu- kocyte antigens: A1; A32; B52; YDR 7; DR8; DR52; DR53; DQ2; DQ4. During phlebitis episodes, the eryth- rocyte sedimentation rate was 32 mm (normal range <15 ram); the leukocytosis value was 10,200 cells/~l (normal range 4800 to 8500 cells/~zl). There was one episode of an increase in ~2-globulin values, with a value of 14.3% (normal range 7.00% to 13.00%). All other data were within the normal range.

M A T E R I A L A N D M E T H O D S

Representative samples of aortic and right com- mon femoral arteries were fixed in 2.5% glutaralde- hyde and postfixed in 1% osmium tetroxide. After ethanol dehydration, the samples were embedded in araldite. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a Philips 400 T transrnission electron microscope (Philips Electronic Instruments, Inc., Mahwah, N.J.).

R E S U L T S

Aorta. Ultrastructurally, smooth muscle cells and inflammatory cells (i.e., lyrnphocy~es, macro- phages, and polymorphonuclear leukocytes) were observed in the aneurysmal wall. Smooth muscle cells frequently showed prominent and dilated cis- ternae of rough endoplasmic reticulum, thus re- sembling rnyofibroblasts. The extracellular matrLx components showed degenerative changes. In par- ticular, elastic fibers were reduced significantly in number and displayed a frayed appearance. Abun- dant filamentous proteoglycans were also present. Capillary channels were often occluded by bulging endothelial cells with degenerative features (Fig. 3). Frankly necrotic endothelial cells were also ob- served. Perivascular infiltrates of lymphocytes and polymorphonuclear leukocytes were a common finding (Fig. 4).

R igh t c o m m o n femoral artery. The samples showed findings similar to those observed previously in the aorta. However, in this case rnyofibroblasts predominated over inflammatory cells. Further de- generating endothelial cells were not found. Inter- estingly, filamentous proteoglycans were observed within dilated cisternae of rough endoplasmic retic- ulum (Fig. 5). The extracellular matrix contained bundles of collagen fibers and a great number of proteoglycan particles (Fig. 6). Minute collections of spiny collagen were also observed (Fig. 6, inset). No elastic tissue was seen.

764 Freyrie et aL JOURNAL OF VASCULAR SURGERY

April 1993

Fig. 2. Digital subtraction angiogram of right common femoral artery false aneurysm.

DISCUSSION The patient presented herein had five aneurysms

in 6 years, two of which were true aneurysms, two anastomotic aneurysms, and one at the site of an angiographic puncture. The diagnosis of Behqet,s disease was formulated as a result of the simultaneous presence of recurrent oral ulceration, recurrent gen- ital ulceration, and skin lesions, in agreement with the diagnostic criteria of the International Study Group for Beh~et's disease. 6 This patient presents character- istics typical of a patient with Beh~et's disease regarding young age, male sex, early onset of symptoms, and multiple recurrences. 7

The ultrastrucmral investigation confirms previ- ous suggestions s'9 concerning the crucial role of vasculitis in the development of aneurysmal compli- cations in Beh~et's disease. The observation of degenerative and necrotic endothelial cells, along with perivascular inflammatory cells including poly-

morphonuclear leukocytes, could be related to the cytotoxic effect of released free oxygen radicals from activated neutrophils, as originally suggested by Niwa et al}0 Furthermore, the loss of elastic tissue accompanied by massive collagen deposition may progressively lead to destruction of the media and therefore to the formation of a true aneurysm. 4011

The development of an aneurysm that was apparently related to an arterial puncture may be a consequence of the myxoid changes that we have documented in the tight common femoral arterial wall. This may lead to the speculation that r emod(~ ing of the extracellular matrix is suboptimal in Behqet's disease, thus rendering the arterial wall particularly susceptible even to very low-entity trauma.

Although such ultrastructural characteristics are similar between the aortic and femoral artery aneu- rysm, an extracellular reparative process with myxoid aspects is present in the latter. This process does not show vasculitis and there is little inflammatory infikrate.

Nowadays the surgical 4,7,11 and nonsurgica113 techniques proposed for the treatment of aneurysms in Beh~et,s disease do not ensure definitive repair if the disease is in an active phase. Some authors 7'12'14 have suggested performing a bypass with anasto- moses on "intact" arteries, far away from the aneu- rysms, or performing an extraanatomic bypass. W~ do not agree with this theory for two reasons: first, it is not possible to identify an intact segment of artery. This is demonstrated by the fact that pseudo- aneurysms could develop at the site of an angio- graphic puncture. Second, by performing two anas- tomoses, the grafting would increase the risk of aneurysmal complications.

Barlett et al.4 described a clinical case in which 14 aneurysms developed in different periods. Some of them were false aneurysms that had arisen as grafting complications. A right iliac artery aneurysm was treated by aneurysmorraphy without recurrence at the 2-year follow-up. Kingston et al. s reported one femoral artery true aneurysm that was treated b~ ~ direct aneurysmorraphy without recurrence at the 1-year follow-up. In the same patient a right axillary false aneurysm was treated by the same technique and developed a new false aneurysm after 35 days. A new direct repair of the aneurysm was performed and did not lead to any further complication. In the same way, we did not observe any consequence at the 6-year follow-up after repair of the true aortic aneurysm. Grafting procedures performed in this patient in another institution have often been accom-

JOURNAL OF VASCULAR SURGERY Volume 17, Number 4 Frcyrie et al. 765

Fig. 3. Hypertrophic endothelial cell (asterisk) line of a microvascular channel. Scattered lymphocytes are evident in perivascular space. (Original magnification × 29,000.)

Fig. 4. Remnants of endothelial cells are associated with inflammatory cells (arrow). Residual pericyte (asterisk) is also present. (Original magnification × 8000.)

partied by formations of anastomotic aneurysms. On the basis o f these data, we support a surgical approach with simple aneurysmectomy and closure of the arterial defect by direct suture or patching. This technique: seems to be compatible with the morphol- ogy of the false and saccular aneurysms of Beh~efs disease. When possible, arterial protection by pros- thetic wrapping would be useful.

This c.ase presents three peculiar characteristics:

(1) The three basic types of aneurysmal pathologic elements in Beh~et's disease (true, anastomotic, and postangiographic) are included in the same patient. (2) Although careful pathologic studies on the aneurysms in Beh~et's disease have been published, 1° the ultrastructural characterization of true and false aneurysms has not been described previously, to our knowledge. For this reason we were not able to perform any morphometric comparative analysis. (3)

JOURNAL OF VASCULAR SURGERY 766 Freyrie et al. April 1993

Fig. 5. Left, Portion of myofibroblast (218) displays dilated cisternae of rough endoplasmic reticulum. Bundles of contractile filaments are displaced peripherally. (Original magnification ×20,000.) Right, Vacuoles containing proteoglycan particles are observed within cell cytoplasm (arrow). (Original magnification × 56,000.)

Fig. 6. Extracellular space is comprised of sparse elastic fibers (EL), a loose collagen (C) network entrapping an evident proteoglycan matrix. Note some giant proteoglycan particles (arrow). Inset shows a few "spiny" collagen fibrils (arrow). (Original magnification × 57,000; inset × 56,000.)

The length o f follow-up o f our case, regarding the direct aortic aneurysmorraphy, is suffident (6 years) to determine the efficacy of this technique. Moreover, during this period the disease was still active, as demonstrated by the development of a new aneurysm in the femoral artery.

We thank Ms. Susan West for revising the English text of this manuscript.

REFERENCES 1. Behqet HH. Uber Rezidivierende, Apthose, dutch ein Virus

verursachte geschwure am Mund, am Auge unde un der Genitalen. Dermatol Wochenschr 1937;105:1152-7.

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2. Mishima Y, Ishikawa K, Kawase S. Beh~et's syndrome with aneurysms [Abstract]. lpn Circ I 1961;25:1211.

3. Kingston M, Ratcliffe IR, Alltree M, Merendin KA. Aneu- rysms ~&er arterial puncture in Beh~et's disease. Br Med I 1979;1:1766-7.

4. Barlett ST, McCarthy WI, Palmer AS, Flinn WR, Bergan II, Yao IS. Multiple aneurysms in Beh~et's disease. Arch Surg 1988;123:1004-8.

5. Ozer 7G, Cetin H, Kahraman C. Thrombophlebitis in Beh~et's disease. Vasa 1955;14:379-82.

6. International Study Group for Beh~et's disease. Criteria for diagnosis of Behset's disease. Lancet 1990;335:1078-80.

7. Sherif A, Stewart P, Mendes D. The repetitive vascular catastrophes of Beh~et's disease: a case report with review of the literature. Ann Vasc Surg 1992;6:85-9.

8. yahama K, Kosuga K, Kinoshita H, et al. Vasculo-Beh~et's disease: immunological study of the formation of aneurysrns. l Cardiovasc Surg 1988;29:751-5.

9. Katoh K, Matsunaga K, Ishigatsubo Y, et al. Pathologically defined neuro-entero-Behqet's disease. J Rheumato11985; 12: 1186-913.

I0. Niwa J, Hiyake S, Sakane T, Shingu H, Yokoyama M. Autooxidative damage in Beh~et's disease: endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils. Clin Exp Immunol 1982;49:247- 55.

11. Matsumoto T, Vekusa T, Fukuda Y. Vasculo-Behqet's disease: a pathologic study of eight cases. Hum Pathol 199i;22:45- 51.

12. Challlou P, Patra P, Noel SF, DeFrancal P, Planchon B, Sagan C. Behqet's disease revealed by double peripheral arterial involvement. Ann Vasc Surg 1992;6:160-3.

13. Smith EJ, Abulafi H, McPherson GA, Allsion DI, Mansfield AO. False aneurysms of the abdominal aorta in Beh~et's disease. Eur I Vasc Surg 1991;5:481-4.

14. Dundar-Kaldirinci SV, Ares KB, Aklopat T, Nazli H. Iliac artery aneurysm in Beh~et's disease: a case report. Angiology 1985;36:549-51.

Submitted Feb. 5, 1992; accepted May 27, 1992.

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