Renal Beh[ccedil]et's disease: A cumulative analysis

Renal Behcet’s Disease: A Cumulative Analysis

Tekin Akpolat, Mustafa Akkoyunlu, Ilkser Akpolat, Melda Dilek,

Ali Riza Odabas, and Seza Ozen

Objective: To analyze cumulated data about renal involvement in Behcet’s

disease (BD) and to report on 6 patients with BD and renal problems.

Methods: We found reports of 159 patients (including our patients) with BD

and specific renal disease (amyloidosis 69, glomerulonephritis [GN] 51, renal

vascular disease 35, and interstitial nephritis 4) in our survey.

Results: The frequency of renal problems among BD patients has been

reported to vary between 0% to 55%. Male gender is a risk factor for all types

of renal BD. Nephrotic syndrome was present in 83% of patients with amy-

loidosis, and renal failure was common at the time of diagnosis. The mean

interval between the initial manifestation of BD and diagnosis of amyloidosis

was shorter in men than in women (P � .02). AA-type amyloid fibrils were

shown in all cases studied. Vascular involvement was common in the patients

with amyloidosis (60%). The renal findings in GN show a wide spectrum, from

asymptomatic hematuria and/or proteinuria to rapidly progressive GN. Several

types of glomerular lesions ranging from minor glomerular changes to cres-

centic glomerulonephritis are observed in BD. The common types of glomer-

ular lesions among the reported cases are crescentic GN, proliferative GN, and

immunoglobulin A (IgA) nephritis. Aneurysms may be located throughout the

renal artery, from the orifice of the main artery to intrarenal microaneurysms.

Another type of renal disease (amyloidosis or GN) and other major vascular

involvement were present in all cases with renal vein thrombosis. Hyperten-

sion is common among patients with renal artery aneurysm or stenosis.

Microscopic vascular disease was described in 4 patients.

Conclusions: Based on data in the literature, we suggest that renal involve-

ment in BD is more frequent than has been recognized, although it is most

often mild in nature. Amyloidosis is one of the prognostic factors affecting

survival. Patients with vascular involvement carry high risk for amyloidosis,

and administration of colchicine to these patients may be beneficial. More

evidence is needed to accept interstitial nephritis as a manifestation of BD. In

spite of some difficulties, hemodialysis and renal transplantation are safe

treatment options in BD-related uremia.

Semin Arthritis Rheum 31:317-337. Copyright 2002, Elsevier Science (USA).

All rights reserved.

From the Ondokuz Mayıs University School of Medicine,Samsun-Turkey, Yale School of Medicine, New Haven, CT;Ataturk University School of Medicine, Erzurum-Turkey; andHacettepe University School of Medicine, Ankara-Turkey.Tekin Akpolat, MD:Professor, Department of Nephrology,

Ondokuz Mayıs University School of Medicine, Samsun-Tur-key;Mustafa Akkoyunlu, MD, PhD:Postdoctoral fellow, De-partment of Rheumatology, Yale School of Medicine, NewHaven, CT;Ilkser Akpolat, MD:Associate Professor, Depart-ment of Pathology, Ondokuz Mayıs University School of Med-icine, Samsun-Turkey;Melda Dilek, MD:Resident, Departmentof Internal Medicine, Ondokuz Mayıs University School of

Medicine, Samsun-Turkey;Ali Riza Odabas, MD:AssistantProfessor, Department of Nephrology, Atatu¨rk UniversitySchool of Medicine, Erzurum-Turkey;Seza Ozen, MD:Profes-sor, Department of Pediatric Nephrology, Hacettepe UniversitySchool of Medicine, Ankara-Turkey.Address reprint requests to Tekin Akpolat, MD, Ondokuz

Mayıs Universitesi, Tıp Faku¨ltesi, Nefroloji Bilim Dali, Sam-sun-Turkey 55139. E-mail: [email protected] 2002, Elsevier Science (USA). All rights reserved.0049-0172/02/3105-1076$35.00/0doi:10.1053/sarh.2002.31721

317Seminars in Arthritis and Rheumatism, Vol 31, No 5 (April), 2002: pp 317-337

INDEX WORDS: Behcet’s disease; amyloidosis; glomerulonephritis; renal vas-

cular disease; interstitial nephritis; uremia.

BEHCET’S DISEASE (BD) is a multisystemdisorder characterized by vasculitis (1). It

was first described by Hulusi Behçet in 1937 andconsists of a triad of recurrent ulcers of the oral andgenital mucosa with relapsing uveitis. Since its firstdescription, additional organ involvement has beendocumented, including the skin, central nervoussystem, and pulmonary tree. Subcutaneous throm-bophlebitis, deep vein thrombosis, epididymitis,arterial occlusion and/or aneurysms, arthralgia, ar-thritis, family history, and gastrointestinal prob-lems are other features of BD (2-9).Conflicting reports in the literature suggest that

renal involvement of BD is not a unanimouslyaccepted complication of BD. In an article pub-lished in 1975, Chajek and Fainaru (10) stated that“B.D. does not affect the kidney.” Their statementwas based on an evaluation of the clinical findingsreported in 683 published cases. Many comprehen-sive review articles about BD do not include renalinvolvement among the organs affected (11-12). Attimes, renal involvement has been cited in letters tothe editor (13-15). Despite this lack of recognitionand importance, several renal problems have beenassociated with BD and can be divided into 5groups: 1) glomerulonephritis (GN), 2) amyloid-osis, 3) renal vascular involvement, 4) interstitialnephritis (IN), and 5) other problems, such ascomplications of drug therapy or genitourinarysystem abnormalities (16-119). Most articles de-scribing the renal complications of BD are pre-sented as case reports.The number of studies evaluating histopatho-

logic findings of renal problems in BD are limited.Data about histopathologic findings of renal BDwere mainly obtained from 2 studies. Beaufils et al(23) assessed renal biopsy findings of 11 patientswithout symptoms of renal disease and found thatin spite of 5 patients having proteinuria (one 2 g/d,others between 0.2 and 0.4 g/d), 8 patients hadfibrinoid electron-dense mesangial and irregularsubepithelial deposits, and 10 patients had positiveimmunofluorescence for C3 in the mesangium andalong the capillary basement membrane. The pa-tient with a proteinuria of 2 g/d had focal andsegmental GN. Arteriolosclerosis was present in allcases. These findings were republished by Herre-

man et al (24) in an another journal 2 years later. Ina review of 170 Japanese autopsied BD cases, 60(35%) patients had renal alterations, whereas 7 hadnephritis (7). Other pathologically defined renallesions were pyelonephritis (n� 23), nephroscle-rosis (n� 8), urolithiasis, renal infarct, and renalcongestion. Patients with nephritis and pyelone-phritis were not clinically characterized, and de-tailed histopathologic examination findings werenot reported.A study designed to evaluate the clinical char-

acteristics, prognosis, and treatment of patientswith renal BD has not been conducted previously,and most review articles and textbook chapters donot provide information about these topics (120-121). The objectives of this study were to 1) report6 patients with BD and renal problems, 2) deter-mine the frequency of renal problems in BD, and3) discuss lesser known features of renal BD suchas clinical characteristics, prognosis, and treatmentoptions with respect to the previously publishedcases.

MATERIALS AND METHODS

Presentation of Cases

Six patients (5 men and 1 woman; mean age, 36years; range, 20-60 years) with BD and renalproblems were included in the study. These pa-tients were referred from departments of dermatol-ogy, urology, and cardiovascular surgery. Cases 1and 2 had been reported previously (58-59). Allpatients had fulfilled the International Study GroupCriteria (122) for the diagnosis of BD. The signif-icant renal features of these cases are summarizedbelow.Case 1. A 26-year-old man presented with

oral and genital aphthae, erythema nodosum, andthrombophlebitis in 1986, and colchicine treatmenthad been initiated for a diagnosis of BD (58). In1990, edema and diarrhea developed. At that time,physical and laboratory examinations showed ne-phrotic syndrome, obstruction of the vena cavainferior, end-stage renal failure, and AA-type amy-loidosis by rectal biopsy. The patient had under-gone 2 unsuccessful operations for arteriovenousfistula. Subsequently, he began regular hemodial-ysis treatment after a successful arteriovenous fis-

318 AKPOLAT ET AL

tula operation that remained functional. After theinitiation of hemodialysis, the activity of BD de-creased, and he was free of oral aphthous ulcer-ations as of May 2001.Case 2. A 43-year-old-man was hospitalized

because of edema of the lower extremities 6months before his admission in August 1998 (59).He had oral and genital aphthae, erythema nodo-sum, uveitis, and a positive pathergy test in 1985-1986; colchicine and corticosteroids were admin-istered for a diagnosis of BD. Steroid treatmentwas discontinued after the uveitis improved, and hedid not receive colchicine regularly. In 1994, ar-thritis, subcutaneous thrombophlebitis, and deepvein thrombosis developed. Warfarin treatmentwas initiated for vascular involvement. On admis-sion in 1998, physical examination showed oralaphthous lesions, edema of the lower extremities,and muscle atrophy. Laboratory studies disclosedblood urea nitrogen, 3.3 mmol/L; serum creatinine,62 �mol/L; and serum albumin, 27 g/L. Urinaryprotein excretion was 3.8 g/d. Renal biopsyshowed AA-type amyloidosis. The patient wasadministered regular colchicine treatment. Sincethen, the edema resolved, but his serum albuminlevel manifested a transient increase. Currently, hisnephrotic syndrome persists.Case 3. A 20-year-old man was admitted to

the hospital because of macroscopic hematuria in2000. He had oral aphthae for 7 years. Otherclinical findings of BD were papulopustular le-sions, arthritis, and a positive pathergy test. Bloodurea nitrogen, serum creatinine, and serum albu-min concentrations were normal, but microscopichematuria was noted. Renal biopsy showed focalproliferative GN and treatment with low-doseprednisolone (10-20 mg/d), dipyridamole, and col-chicine was administered. During 10 months offollow-up, he had intermittent microscopic hema-turia and proteinuria (25 mg/dL).Case 4. A 25-year-old woman was admitted to

the hospital because of asymptomatic proteinuriaand hypertension. She had oral aphthous lesionsfor 6 years. Other clinical findings of BD weregenital ulcerations, acneiform nodules, erythemanodosum, arthritis, subcutaneous thrombophlebi-tis, and a positive pathergy test. Laboratory studiesdisclosed normal blood urea nitrogen, serum cre-atinine and serum albumin concentrations, micro-scopic hematuria, and proteinuria (1.2-2.5 g/d).Renal biopsy showed focal and segmental glomer-

ulosclerosis. Treatment consisting of low-doseprednisolone (10-20 mg/d), angiotensin-convertingenzyme inhibitor, and colchicine was initiated.Proteinuria (ranging from 0.8-1.5 g/d) and micro-scopic hematuria persisted 9 months later.Case 5. A 43-year-old man had intermittent

microscopic hematuria and proteinuria (280 mg/d).Clinical findings of BD were oral and genitalulcerations, papulopustular lesions, and arthralgia.Abdominal ultrasonography and intravenous urog-raphy findings were unremarkable, and renal bi-opsy was not performed.Case 6. A 60-year-old man was referred from

the Department of Cardiovascular Surgery becauseof end-stage renal failure. His previous historyincluded BD for 38 years and diabetes mellitus for15 years. Clinical findings of BD were oral andgenital aphthae, acneiform nodules, ocular in-volvement, erythema nodosum, thrombosis of deepveins, and arthritis. BD activity was negligiblesince 1990 except for oral aphthous ulcerations,which had been last observed 2 years before. Theonset of renal failure was not clear, but the cause ofend-stage renal failure was probably diabetes mel-litus. Femoral and subclavian vein catheterizationswere unsuccessful because of vascular BD. Pri-mary failure was observed in the first arteriovenousfistula operation. The patient began regular hemo-dialysis treatment after the second arteriovenousfistula operation in August 2000, and he was alivein June 2001.

LITERATURE REVIEW

Methods

We conducted a comprehensive review of theliterature to analyze cumulated data about renalinvolvement in BD. The PubMed, OVID, MdCon-sult, and Web of Science databases were searchedfor articles using the terms BD or Behçet’s syn-drome combined with 1 of the following terms:amyloidosis, renal involvement, renal disease, ne-phritis, renal artery,and renal vein. Pertinent ar-ticles cited as references in the identified papersalso were reviewed.We identified 155 patients with BD and specific

renal disease, and clinical data were available from132 patients. Table 1 shows the types of renalinvolvement in 159 patients including our 4 pa-tients. Five languages (English, Japanese, French,Spanish, and Turkish) were used in the articles

319RENAL BEHCET’S DISEASE

about previously reported patients. Clinical datawere presented in 132 of the 155 patients, and wecould find reports of 128 cases (97%) in our librar-ies. Some clinical data were obtained in the re-maining 4 patients (34,70,85,87) in the referencesciting them (38,75,77). Some patients were re-ported more than once (23,24,61-64,67,68,80,81).There were an additional 41 BD cases with renal

problems, and they could be categorized into 3groups: 1) 15 cases in which renal disease was notclearly defined because renal biopsy or renal an-giography was not performed (49,55,63,77,123-125), 2) 6 patients with proteinuria and/or hema-turia but without any pathologic abnormalities inrenal biopsy (42,126), and 3) 20 patients withglomerular changes determined on renal biopsywithout description of the type of glomerular dis-ease or clinical characteristics of the patients(57,91,127,128). These 41 cases were not includedin the study.

Statistics

Mann-WhitneyU test and�2 test with Yates’correction were used for statistical analysis. TheKaplan Meier technique was used to assess sur-vival rates of patients with BD and amyloidosis.Cases diagnosed by necropsy were excluded, andlast visit was accepted as the final date for thelost-to-follow-up time.

RESULTS

Clinical characteristics of our patients and thosewith available clinical data in the literature areshown in Tables 2 to 4 and are summarized below.

Amyloidosis

The mean age of patients with amyloidosis was36.5 years (range, 13-70 years), and 54 (84%) ofthe 64 patients were male. The mean interval

Table 1: Analysis of Patients With BD and Renal Involvement

Type of Renal Involvement No. of Cases

No. of Cases With

Available Clinical Data Reference No.

Amyloidosis 69 64 42, 50, 55, 58-92Glomerulonephritis 51 51 16-57Renal vascular diseaseMacroscopic vascular diseaseRenal artery aneurysm 12 8 2, 93-102Renal arterystenosis/occlusion 12 2 2, 7, 57, 90, 102-104

Renal vein thrombosis 7 4 2, 37, 63, 79, 83, 105Microscopic vascular disease 4 4 49, 106-108

Interstitial nephritis 4 3 109-113Total 159 136

Table 2: Clinical Features of Patients with

BD and Amyloidosis

Clinical Feature

Positive/No.

Available %

Oral ulceration 62/62 100Genital ulceration 55/62 89Skin involvement 37/58 64Ocular involvement 37/58 64Pathergy test 20/27 74Arthritis/arthralgia 28/57 49Vascular involvement 34/57 60CNS involvement 12/57 21GIS involvement* 1/55 2Renal symptoms/signs†Proteinuria (more thantrace) 52/58 90

Nephrotic syndrome 48/58 83Hematuria 7/30 23Leukocyturia 3/24 13Hypertension 5/34 15Renal failure 29/56 52

AA type of amyloidosis 28/28 100HLA-B(51)5 15/20 75

Abbreviations: CNS, central nervous system; GIS, gastrointes-tinal system.*GIS involvement other than amyloidosis.†At presentation or during disease course.

320 AKPOLAT ET AL

between the initial manifestation of BD and thediagnosis of amyloidosis was 9.6 years (range, 1.3to 27 years) and was significantly shorter in malesthan in females (9 yearsv 13 years;P � .02).Vascular involvement (venous thrombosis, subcu-taneous thrombophlebitis, arterial aneurysms,and/or occlusions) was common (60%, 34/57).Figure 1 shows the cumulative survival time ofpatients with amyloidosis; the 5-year survival ratewas 46%.

Glomerulonephritis

The mean age of patients with GN was 37 years(range, 13-70 years) and 34 (72%) were male. Themean interval between the initial manifestation ofBD and the diagnosis of GN was 8 years (range, 2months to 22 years) and was shorter in femalesthan in males (5.9 yearsv 8.8 years,P� .05). GNpreceded the diagnosis of BD in 2 cases (28,43).Arthritis and arthralgia were common (71%, 32/45).

Renal Vascular Disease

Renovascular BD (lesions located throughoutthe renal vascular system) can be classified into 2groups according to the site of involvement: mac-roscopic (predominantly middle-sized arteries andveins) and microscopic (predominantly small ar-teries, arterioles, capillaries, and venules) vasculardisease. We found 35 cases with renal vasculardisease (Table 1). All patients with renal arteryaneurysms were men (mean age, 32 years; range,21-42 years). The interval between the onset ofinitial manifestation of BD and the detection ofrenal artery aneurysm was between 2 and 10 years(mean, 5 years) except for 1 patient whose initialBD manifestation was pulmonary artery aneurysm(97); other symptoms or signs of BD were notpresent in this patient at the time of presentation.Other than this patient, the clinical characteristicsof BD were reported in 6 patients. Four of the 6patients (67%) fulfilled the International StudyGroup Criteria (122) for the diagnosis of BD. Allhad oral aphthous ulcerations, 5 (83%) had ocular

Table 3: Literature Review of BD-Related GN Based on the Pathologic Diagnoses of the Authors

Type of Glomerular Disease n Reference No.

Diffuse proliferative GN (IgA) 6 18, 31-33, 36, 38Diffuse proliferative GN 5 22, 26, 30, 40, 54Crescentic GN 5 25, 36, 36, 49, 53Focal proliferative GN 5 16, 27, 57, 57, Case 3Mesangial proliferative GN 3 46, 55, 55Minor glomerular lesion 3 34, 42, 45Focal proliferative GN (IgA) 2 21, 29Membranoproliferative GN 2 26, 52Membranous GN 2 28, 56Minimal change GN 2 37, 50Focal proliferative and necrotizing GN 2 17, 19IgA nephritis 2 42, 42Focal segmental GN 2 23, 51Focal segmental GN (IgA) 1 47Focal sclerosing GN 1 42Mesangiocapillary GN (IgA) 1 48Mesangial GN 1 50Focal proliferative and sclerosing GN 1 55Focal segmental necrotizing GN 1 20Focal segmental necrotizing GN (IgA) 1 35Focal necrotizing GN 1 39Glomerulosclerosis 1 44Focal and segmental glomerulosclerosis 1 Case 4


involvement, 4 (67%) had genital aphthous ulcer-ations, 3 (50%) had skin involvement, and 2 of5(40%) had arthritis. Other major vascular diseasewas present in 4 of the 6 (67%) patients. Bloodpressure measurements were reported in 5 patients:4 had hypertension and 1 had hypotension becauseof rupture of an aneurysm. Proteinuria and hema-turia were not present in the 3 patients whose urinefindings were reported. Mild renal failure waspresent in 2 patients with intrarenal microaneu-rysms. Bilateral renal involvement was detected in3 of the 6 (50%) patients.All patients with renal vein thrombosis were

male. Their clinical characteristics were as follows:mean age, 35.7 years (n� 3); oral aphthous ulcer-ations, 100% (4/4); genital aphthous ulcerations,100% (4/4); ocular involvement, 75% (3/4); acne-iform lesions, 25% (1/4); arthralgia/arthritis, 50%(2/4); central nervous involvement, 25% (1/4);hypertension, 0% (0/3); hematuria, 33% (1/3); ne-

phrotic syndrome, 100% (4/4); and renal failure25% (1/4). Renal failure developed in an anotherpatient a few months later. Other types of renaldisease (amyloidosis in 3 patients and minimalchange disease 1 patient) and other major vascularinvolvement (inferior vena cava thrombosis in 3patients and right cerebral thrombosis in 1 patient)were present in all cases. The mean interval be-tween the initial manifestation of BD and thedetection of renal vein thrombosis was 12 years(n � 2).Sufficient clinical data were reported in 2 of the

12 patients with renal artery stenosis. The firstpatient was a 39-year-old man who had fulfilledthe International Study Group Criteria (122) for thediagnosis of BD. He had hypertension, and arte-riographic examination showed renal artery steno-sis at the orifice of the left renal artery. In thesecond case, renal artery stenosis was detected in a9-year-old hypertensive boy, and the diagnosis ofBD was made 17 years later when he manifestedother signs of BD.Microscopic vascular disease was described in 4

patients. Their clinical characteristics were as fol-lows: mean age, 39 years (n� 2); male, 100%(4/4); oral aphthous ulcerations, 100% (4/4); gen-ital aphthous ulcerations, 67% (2/3); ocular in-volvement, 50% (1/2); acneiform lesions, 100%(2/2); other vascular disease, 0% (0/2); arthralgia/

Table 4: Clinical Features of Patients With

BD and GN

Clinical Feature

Positive/No.

Available %

Oral ulceration 46/46 100Genital ulceration 38/46 83Skin involvement 31/40 78Ocular involvement 23/40 58Pathergy test 10/19 53Arthritis/arthralgia 32/45 71Vascular involvement 15/43 35CNS involvement 8/45 18GIS involvement 3/42 7Family history 0/39 0Renal symptoms/signs*Proteinuria†Absent or trace 3/46 7�3 g/d 24/46 52�3 g/d 19/46 41

Hematuria 36/42 86Pyuria 13/41 32Hypertension 11/42 26Renal failure 21/46 46

HLA-B(51)5 7/17 41

Abbreviations: CNS, central nervous system; GIS, gastrointes-tinal system.*At presentation or during disease course.†Modified to include current data.

Fig 1. Cumulative survival rate of patients with

Behcet’s disease and amyloidosis.

322 AKPOLAT ET AL

arthritis, 100% (2/2), central nervous involvement,50% (1/2); hypertension, 0% (0/3); positive pathergytest, 50% (1/2); hematuria, 67% (2/3); mild pro-teinuria, 67% (2/3); renal failure, 0% (0/3); andHLA B5 100% (2/2). The mean interval betweenthe initial manifestation of BD and the diagnosis ofmicroscopic vascular disease was 3 years (range, 1month to 6 years).The clinical characteristics of the patients with

BD and IN are presented in the Discussion.

DISCUSSION

Proteinuria and hematuria associated with BDwere first reported in 1963 (126). Subsequently 2patients with BD and renal problems were de-scribed (125). The first histologic diagnosis of GNwas provided in 1973 (16). The first diagnosis ofBD–related amyloidosis was made in 1958 at nec-ropsy, and this case was published in 1964 (62). In1980, the diagnostic criteria of Zhang includedurinary problems (renal damage, ulceration ofbladder, hematuria, epididymitis) as minor criteriafor BD (129-130). Although many patients withBD and renal problems have been presented in theliterature, a cumulative analysis of these cases hasnot been reported previously. The frequency ofrenal problems may be estimated from previousreports and varies from 0% to 55% (Table 5). Thecause of this wide variation is not known, butlimited evaluation probably is a contributing fac-tor. The frequency of renal problems is high incohort studies (42,90,126,131). Rosenthal et al(90) evaluated urinalysis records of 77 patientsretrospectively (urinalysis records were availablein only 33 patients) and of 51 patients prospec-tively. Proteinuria and/or microhematuria wasfound in 25 (32%) of the 77 patients.Although numerous reports associate renal prob-

lems with BD, some patients likely do not have thesymptomatology that would lead physicians to ex-amine them for renal disease. Our analysis showedthat the most common renal problems in BD wereasymptomatic hematuria and proteinuria, followedby amyloidosis and GN. Renal vascular involve-ment was less frequent, and interstitial nephritiswas rare.

Amyloidosis

Since 1964, 69 cases with BD and amyloidosishave been reported. The frequency of amyloidosisamong BD patients varies between 0.01% to 4.8%

in different series (42,49,55,66,71,77-81,90,92,150).Most cases derive from the Mediterranean and Mid-dle East regions compared with Japan (60 casesv 5cases).The clinical manifestations of amyloidosis vary

widely and depend on the organ system involved.The diagnosis of amyloidosis is based on biopsy ofthe involved tissue, and AA-type amyloid fibrilshave been shown in all biopsy specimens exam-ined either by the potassium permenganate methodor immunohistochemistry using monoclonal anti-bodies. Nephrotic syndrome was present in most ofthese patients, and renal failure was common at thetime of diagnosis. On the other hand, 6 patientswith amyloidosis had trace proteinuria or did nothave any proteinuria (61,73,75,77,82,84).Vascular involvement is one of the dreadful

manifestations of BD and is related to diseaseseverity. The relationship between vascular in-volvement and amyloidosis in BD has not beenpreviously investigated. The present analysis in-cludes cases from many countries/regions andshows that vascular involvement is commonamong patients with BD and amyloidosis (60%),nearly all of whom had major vascular problems.Studies performed in Turkey (n� 2,147), Iran(n � 3,153), Japan (n� 3,316), and Europe (n�714) have shown that the frequencies of vascularinvolvement in BD were 17%, 9%, 9%, and 10%to 37%, respectively (12,105,127,132). The fre-quency of vascular involvement is significantlyhigher in BD patients with amyloidosis than inthose without amyloidosis if we compare our find-ings with these studies (�2 � 10, P � .01 for allcomparisons).Although Rosenthal et al (61) suggested that

amyloidosis may be an intrinsic feature of BD, wecould not find any report in which amyloidosispreceded the development of BD. The intervalbetween the onset of the first symptom of BD andthe diagnosis of amyloidosis ranged from 16months to 27 years and was significantly shorter inmen than in women. This interval was longer than9 years in all women, which is compatible with theless severe course of BD in women. These clinicalobservations and the presence of AA type amyloidfibrils in BD suggest that amyloidosis is secondaryto inflammation.No specific treatment exists for AA-type amy-

loidosis. The principal aim in the treatment ofpatients with AA amyloidosis is to switch off


Table 5: Frequency of Renal Problems in BD

Author

(Reference No.) Country

No. of

Patients

With BD

Frequency

of Renal

Involvement

(%)

Parameter Evaluated

(if Specified)

Sarica (131) Turkey 62 55 Proteinuria31 Hematuria

Rosenthal (90) Israel 77 32 Proteinuria and/or hematuriaShimizu (2) Japan 100 20 Abnormal urine findingsOshima (126) Japan 65 20 Proteinuria and/or hematuriaNumo (42) Italy 45 20 Proteinuria and/or hematuriaShahram (127) Iran* 3,153 11 Abnormal urine sedimentGharibdoost (91) Iran* 2,068 6 Hematuria

4 ProteinuriaZouboulis (132) Europa 714 0-10El Ramahi (55) Saudi Arabia 120 8Mousa (133) Kuwait 29 7Pei-da (134) China 34 6Valesini (135) Italy 155 5Chung (136) Taiwan 103 5Madanat (137) England 150 5 Proteinuria and/or hematuriaWilliams (21) England 38 5Nakabayashi (138) Japan 55 4Kone-Paut (113) International 65 3 Proteinuria and/or hematuriaBen Moussa (49) Tunisia Not available 3Gurler (66) Turkey* 250 2Vaiopoulos (139) Greece* 42 2 GlomerulonephritisKaklamani (3) Greece* 64 2Pande (140) India 58 2 HematuriaBenamour (141) Morocco 285 1 ProteinuriaGurler (105) Turkey* 2,147 �0.1Hamuryudan (40) Turkey �1,300 �0.1 Biopsy proven

glomerulonephritisChajek (10) Israel 41 0 Normal renal function and

urinalysisReview of BDpublished cases

683 0

Ben Hmida (142) Tunisia 46 0 Normal renal function andurinalysis

Chamberlain (143) England 32 0 No renal abnormality definedAssaad Khalil (144) Egypt 180 0 No renal abnormality definedSanchez (145) Spain 30 0 No renal abnormality definedCalamia (146) USA 164 0 No renal abnormality definedSharquie (147) Iraq 58 0 No renal abnormality definedBerrah (148) Algeria 58 0 No renal abnormality definedShukurova (149) Tadjikistan 36 0 No renal abnormality defined

*The same centers.

324 AKPOLAT ET AL

production of serum amyloid A protein by control-ling the underlying disease process. The observa-tion that colchicine may inhibit collagen transportto the extracellular space led physicians to use itfor the prevention and inhibition of amyloid pro-duction and deposition. Colchicine has beneficialeffects in the prevention of amyloidosis in patientswith familial Mediterranean fever (151) and issometimes used in patients with BD (121). Manyphysicians have used colchicine in the manage-ment of BD–related amyloidosis. Only 10 patientswith BD and amyloidosis have recieved colchicinebefore the diagnosis of amyloidosis (50,58,59,77,

81,84). Although colchicine did not alter the pro-gression of amyloidosis in some cases, it wasbeneficial in others, and many researchers recom-mend it in BD-related amyloidosis (Table 6). Five(58,65,77,78,81) of the 6 patients who survivedlonger than 9 years were given colchicine, andtreatment was not specified in the sixth (72). Al-though these numbers are small, they suggest thatcolchicine may be helpful in BD-related amyloid-osis.Vascular and central nervous system involve-

ment are 2 major prognostic factors affecting sur-vival in BD (152). Reports about the prognosis of

Table 6: Experience With Colchicine Treatment for the Prevention and Progression of

BD-Related Amyloidosis

Author

(Reference No.)

No. of

Patients Result/Comment

Melikoglu (81) 14 9- and 11-year survival in 2 patients50% mortality at 3.4 year (range, 1-11)5-year patient survival 52% (estimated from reported data)Use of immunosuppressives and colchicine before or afterthe diagnosis of amyloidosis did not seem to affect theclinical course of amyloidosis.

Skinner (69) 1 Increase of serum albumin, decrease of edemaEl Ramahi (55) 1 Alive at 34 monthsWechsler (74) 1 No influence on proteinuria

Death at 33 months due to cachexiaCases (76) 1 Stabilization of renal function, regression of anasarcaDilsen (77) 1 Alive at 10 years

1 Patient received colchicine 9 years before diagnosis ofamyloidosis, and proteinuria was absent atpresentation.

Colchicine therapy should be started early and continuedas long as possible in cases of BD, not only fortreatment but also for prevention of amyloidosis.

Tasdemir (79) 6 Improvement both in the activity of BD and in the degreeof proteinuria was observed in 3 of 6 patients.

Colchicine may be useful in some casesAkpolat (58) 1 Alive at 11 yearsAkpolat (59) 1 Alive at 34 months

Edema disappeared, serum albumin level increasedtransiently, and nephrotic syndrome persisted.

Hamza (78) 1 No influence on proteinuriaDeath at 3 years in a state of cachexia

Hamza (65) 1 Alive at 13 yearsBen Moussa (49) 2 Clinical remissionMohammadi (88) 2 No influence on proteinuria or uremiaSozen (73) 1 No information


patients with BD and amyloidosis are rare: only 35patients have been followed. Our analysis showsthat the 5-year survival rate is 46%. Sixteen pa-tients died, and 50% of deaths occurred within 2months of the diagnosis of amyloidosis. Amyloid-osis was diagnosed in 6 cases by necropsy. Renalfailure was present in many patients at the time ofdiagnosis. These findings indicate that amyloidosisis another prognostic factor affecting survival inBD and show the importance of early diagnosisand prevention of amyloidosis.

Glomerulonephritis

Glomerular lesions are probably the most fre-quent type of renal disease observed in BD, andmost are asymptomatic. Immune complexes, IgAdeposition, and antineutrophilic cytoplasmic anti-bodies (ANCA) have been implicated in the patho-genesis of GN (20,23,24,27,32,38,44,45,47), butthe etiology remains elusive.The interval between the onset of initial mani-

festations of BD and the detection of renal prob-lems is shorter in patients with GN (less than 6months in 8 patients) compared with those withamyloidosis. There are 2 case reports in which GNappeared before the manifestations and diagnosisof BD (28,43). The clinical manifestations of thepatients with BD and GN are similar to patientswithout GN (12,105,127,132) (Table 4). Unlikeamyloidosis, the spectrum of renal findings in GNshows a wide variation, from asymptomatic hema-turia and/or proteinuria to rapidly progressive GN.These findings often correlate with histopathologicfindings ranging from minor glomerular changes tocrescentic GN. Most reported cases had severehistopathologic abnormalities (crescents and dif-fuse proliferation), probably a result of overrepre-sentation of cases with clinically significant renaldisease. Immunofluorescence examination of mostof the renal biopsies showed deposition of immu-noglobulin G (IgG), IgA, immunoglobulin M(IgM), and C3 mainly along the capilleries and inthe mesangium (18,20-33,35,36,38,40-43,47-49,53-55). Pauci-immune and ANCA-associated GNhave been reported in 2 cases (44,45). No deposi-tion of immunoglobulins and complement wasdetected in another 3 renal biopsy specimens(26,37,55).Glomerular disease can be clinically silent (in-

sidious) or overt. Clinically silent glomerular dis-ease can be detected by screening for proteinuria

and hematuria, as described by Beaufils et al (23)and Rosental et al (90). Proteinuria and hematuriamay occur simultaneously or in an alternatingfashion. Hypertension and mild renal failure maybe present. Glomerular changes may be severe(31,33,38,40,43,55), and silent glomerular di-sease may progress to overt glomerular disease(27,30,39,53). The prognosis of patients with silentglomerular disease is not known, although it seemsfavorable. The clinical characteristics of patientswith silent glomerular disease have not been stud-ied, and treatment remains enigmatic. There are nopathognomonic features predictive of progressivedisease.Overt glomerular diseases include acute GN,

rapidly progressive GN, nephrotic syndrome, andensuing renal failure. Most reported patients haveovert glomerular disease, and histopathologic di-agnoses of these cases are shown in Table 3. Thecommon types of glomerular lesions are crescenticGN, proliferative GN, and IgA nephritis (52,153).BD-related crescentic GN and IgA nephritis havebeen extensively reviewed previously (36,38,39,53). Tables 4 and 5 show the reported cases and donot reflect the frequency of glomerular lesions andclinical features of patients with BD and GN.The treatment and outcome of BD-related GN

are summarized in the Appendix. There is a ten-dency to prescribe corticosteroids. Other agents(colchicine, cyclophosphamide, cyclosporine, aza-thioprine, and plasmapheresis) have been added insome cases, but more studies are needed to clarifytheir effects on the course of glomerular disease.Short-term renal prognosis is favorable in mostcases, but complete remission is rare, althoughspontaneous remission may occur.

Renal Vascular Disease

Vascular involvement is the leading cause ofdeath in BD, and its prevalence varies between 2%and 37% (2-4,9). Vascular involvement is morefrequent in men than in women (4). Three forms ofvascular disease (venous occlusions, arterial aneu-rysms, and arterial occlusions) are found in BD.Venous lesions occur more frequently than arteriallesions, and subcutaneous thrombophlebitis is themost frequent type of venous involvement. Renalvascular disease was found in less than 1% ofpatients with vascular BD (7 of 728 patients) in areview published in 1992 (4).

326 AKPOLAT ET AL

Macroscopic Vascular Disease

Renal artery aneurysm was the most commontype of renal vascular disease among the reportedpatients (2,93-102). The aneurysms may be at anylocation throughout the renal artery, from orifice tointrarenal microaneurysms. Rupture (94,98,100)and infarct (95,99) may complicate these aneu-rysms, and pseudoaneurysms may occur (94,100).All reported patients were male, and hypertension(mostly severe) was the prominent sign of aneu-rysm formation (93,94,96,99). Aneurysm rupturemay lead to hypotension (98). In 67% of the cases,more than 1 major vessel was involved, and bothrenal arteries frequently (50%) (95,96,99) wereaffected.BD patients with intrarenal microaneurysms and

renal infarction may present a problem with no-menclature and classification. According to theChapel Hill classification (154), patients with in-trarenal microaneurysms fulfill the criteria for clas-sical polyarteritis nodosa (PAN). Because the an-tineutrophilic cytoplasmic antibody reactivity isusually negative in patients with classical PAN,there is no reliable diagnostic marker to differen-tiate these 2 types of vasculitis. The authors of 2case reports with intrarenal microaneurysms dis-cussed PAN in the differential diagnosis of theirpatients and stated that some findings were incom-patible with PAN (95,99). A noteworthy feature in1 of the BD patients was the disappearance of theintrarenal microaneurysms without immunosup-pressive treatment (95), which is not expected inPAN. The intervals between the initial manifesta-tion of BD and the detection of intrarenal micro-aneurysms were 6 and 10 years in these 2 patients,which makes the diagnosis of PAN unlikely.Both patients with renal artery stenosis were

men and had hypertension. The hypertension wascorrected by surgical intervention in both patients(57,104).Clinical data were available in only 4 patients

with BD and renal vein thrombosis (37,63,79,83).The striking feature of patients with BD and renalvein thrombosis was the coexistence of anothermajor vascular disease. Thus, patients with ne-phrotic syndrome related to BD should be screenedfor renal vein thrombosis.Angiography and computed tomography (CT)

are commonly used to evaluate arterial and venous

lesions, but they may cause complications. Venouspuncture, intravenous infusion, rapid injection of alarge bolus of contrast material, and insertion of avenous catheter may initiate venous thrombosis inBD. An increased incidence of aneurysm forma-tion at the puncture site has been reported afterarterial puncture (155-157).Magnetic resonance imaging (MRI) and mag-

netic resonance angiography (MRA) are safe, non-invasive, and effective imaging modalities in thediagnosis, evaluation, and monitoring of arterialand venous lesions in patients with BD (157).MRI/MRA may be preferred to angiography andCT in renal vascular lesions, but the ability ofMRI/MRA to show intrarenal microaneurysms islimited compared with angiography. Ultrasonogra-phy also can be used to evaluate renal vesselsbecause of its low cost and easy application, al-though obesity and the presence of bowel gas maypresent some difficulties.No specific treatment is available for renal vas-

cular disease. In general, treatment of arterial dis-ease includes surgical intervention and a combina-tion of corticosteroids and cytotoxic agents such ascyclophosphamide or azathioprine and anticoagu-lants (3,4,12,120,158,159). Anticoagulants with ashort-term course of intermediate doses of corti-costeroids are used for thromboembolic venousdisease (3,12,120). Surgical intervention (nephrec-tomy or embolization or autotransplantation [trans-fer of a kidney from 1 side to another in the samepatient]) was needed in 5 of the 8 patients withrenal artery aneurysm, probably because of latereferral or late diagnosis. Reports about the effi-cacy of immunosupressive and anticoagulant drugsare limited. Winer-Huram et al (97) reported theadministration of coumadin, corticosteroids, andintravenous cyclophosphamide to a patient withrenal artery aneursym; the patient was alive at theseventh month of follow-up. Ariogul et al (99)reported that hypertension was relieved in a patientwith intrarenal microaneurysms after the adminis-tration of an initial dose of 60 mg/d prednisolonetapering to 10 mg/d, 240 mg/d propranolol, and 4.5mg/d prazosin. Improvement of renal vein throm-bosis with heparin and prednisolone was noted in apatient with minimal change GN (37).Data about prognosis of macroscopic vascular

disease is limited, but seemingly the short-termprognosis is not poor. BD should be considered in


the differential diagnosis of intrarenal aneurysmsand renal infarcts and should not be confused withPAN. The coexistence of renal artery aneurysmand renal vein thrombosis with nonrenal vascularBD is observed in most patients; thus, it may bejustified to screen patients with vascular disease forrenal vascular disease with noninvasive methods.The detection of hypertension may lead to earlydiagnosis of renal artery aneurysm and stenosis.Renal vein thrombosis should be considered in thedifferential diagnosis of nephrotic syndrome re-lated to BD. Treatment of macroscopic vasculardisease depends on the site of involvement and thepresence of complications. Surgical intervention isneeded in the management of large aneurysms.Early diagnosis of aneurysms may help improveexperience with immunosupressive and anticoagu-lant drugs.

Microscopic Vascular Disease

Microscopic vascular disease was present in 4cases (49,106-108). These vascular lesions couldnot be explained by atherosclerosis because allpatients were young and normotensive. Hematuriaand/or mild proteinuria were present in all cases.Histopathologic findings were perivascular fibrosisaround interlobular arteries and arterioles and fi-brinoid deposits in vascular walls with minor glo-merular and tubulointerstitial changes. Immunoflu-oresence and electron microscopy findings in 1biopsy showed granular deposits of C3 in thevascular walls and fibrinoid deposits (107).Rebiopsy in 1 patient (108) 6 years later showed

similar histopathologic findings despite the disap-pearance of hematuria. This patient had receivedlow-dose steroids and levamisol treatment. An-other patient was well 10 months after renal biopsy(107). These cases suggest a good prognosis inmicroscopic vascular disease. Microscopic vascu-lar disease may be a cause of asymptomatic andintermittent proteinuria and hematuria, similarto GN.

Interstitial Nephritis

BD is considered in the differential diagnosis ofthe tubulointerstitial nephritis-uveitis (TINU) syn-drome. Beaufils et al (23) described the tubuloin-terstitial changes (edema, fibrosis, tubular atrophy,and few inflammatory cells) observed in BD. Al-though tubulointerstitial lesions may accompany

GN, we found only 4 cases with IN and BD.Almost all articles stating IN as a form of renalinvolvement in BD (35,40,42,49-52,54,72,76,153)cite the same reference (109), but the clinicalcharacteristics of the case were reported elsewhere(110). In this case (a 48-year-old woman), INpreceded the manifestations of BD, and symptomsrelated to BD (oral aphthous lesion and uveitis)appeared during the course of IN. This differs frompatients with GN and amyloidosis in which nearlyall patients had sufficient clinical features for di-agnosing BD before renal problems developed.Thus, other causes of IN should be considered inthis patient. In the second patient (a 50-year-oldman), the diagnosis of IN was made by postmor-tem examination, and clinically significant IN wasnot described (111). Renal biopsy also showedbenign nephrosclerosis. The third reported case (a57-year-old woman) had BD,Escherichia colisep-sis, and megalocytic IN, which is a rare inflamma-tory disorder (112). The pathogenesis of megalo-cytic IN is unclear but is usually associated withgram-negative bacilli infection and/or immuno-logic alterations. The clinical characteristics of thefourth case are unknown (113).These data cast doubt on the association of IN

and BD. More evidence is needed to accept IN asa manifestation of BD, and new additional casereports may clarify this issue.

Other Renal Problems

Hemolytic uremic syndrome/thrombotic throm-bocytopenic purpura related to cyclosporine treat-ment (114,115), cyclosporine nephrotoxicity (53),cyclophosphamide associated carcinoma of the uri-nary bladder (116), neuropathic bladder (117), andinvolvement of the bladder wall (118-119) havebeen reported in patients with BD, and these prob-lems should be considered in the differential diag-nosis of renal involvement. Nonsteroidal antiin-flammatory drugs and interferon are used in themanagement of BD and also can lead to renalproblems.

Renal Failure and BD

Uremia is an occasional complication of renalBD. The effect of uremia on BD activity is notknown. Uremia-related immunosupression mayameliorate BD activity, as with systemic lupuserythematosus (160). Oral and genital aphthous

328 AKPOLAT ET AL

lesions may disappear with uremia or after theinitiation of hemodialysis treatment (case 1) asnoted by Peces et al (72). In addition, we haveobserved that a positive pathergy test was reversedafter the initiation of hemodialysis (case 1).Renal replacement therapy in patients with BD

is associated with a high risk of surgical compli-cations, failure of arteriovenous fistula or grafts,and thrombi at vascular anastomotic sites of thetransplanted kidney (104,157,161,162). The possi-ble beneficial effect of uremia-related immunosu-pression on these vascular problems is not known.Management of renal failure with short-term

peritoneal dialysis was reported in 3 patients(17,60,83). Peritoneal dialysis was complicated byseptic thrombosis of the catheter in 1 of thesepatients (83). Hemodialysis was performed in 16patients (25,26,39-41,53,58,65,72,78,81,83,112,146). Problems related to transient and permanentvascular access for hemodialysis such as earlyfailure of arteriovenous fistulae or grafts wererelatively common (58,83,146), but long-term sur-vival and patency of fistulae or grafts also havebeen reported (58,146).Four cases with BD and renal transplantation (3

allotransplantation, 1 autotransplantation) havebeen reported. Autotransplantation was performedbecause of multiple renal artery aneurysms in 1patient (96). The causes of end-stage renal diseasewere diffuse proliferative GN (40,41) and multipleaortic aneurysms in 2 patients (163). The causewas uncertain in the third patient (163). One pa-tient had thrombi of the inferior vena cava and iliacveins (163); vein to vein anastomosis had beenperformed to the right ovarian vein, an unusualplace for renal transplantation. The pathergy test ischaracterized by a heightened inflammatory re-sponse to simple penetrating trauma and is one ofthe International Study Group diagnostic criteriafor BD (122). Although complications at the anos-tomosis site of the transplanted kidney have notbeen reported, interventions such as puncture ofarteries during angiography or bypass surgery maylead to formation of false aneurysms at the site ofvascu-lar injury or anastomosis (104,157,161,162). Theshort-term prognosis was favorable in these pa-tients. Hemodialysis treatment was initiated in 1patient because of chronic rejection after 6 months(163). The second patient had a functioning graftin the 36th month (163). A third patient received

azathioprine, cyclosporine A, and methylpred-nisolone after transplantation (41). She had normalrenal function and was free of BD symptomsexcept for occasional oral ulcers 40 months afterrenal transplantation.Experience with peritoneal dialysis is limited. In

spite of some difficulties, hemodialysis and renaltransplantation are therapeutic options in BD.

CONCLUSION

The presented data suggests that renal involve-ment in BD is more frequent than has been appre-ciated, although it is most often mild in nature.Male gender is a risk factor for renal BD. Minorglomerular changes and microscopic vascular dis-ease are the 2 most common causes of mild renaldisease. Routine urine examination is needed forthe detection and diagnosis of mild renal disease.Amyloidosis is one of the prognostic factors af-fecting survival, and BD should be considered inthe differential diagnosis of AA-type amyloidosis.Although evidence-based data is insufficient tosupport the use of colchicine in BD-related amy-loidosis, we believe that colchicine may suppressneutrophil inflammation and prevent amyloid dep-osition, as in familial Mediterranean fever. Furtherstudies addressing the effect of colchicine on pro-teinuria, glomerular filtration rate, and patient sur-vival are needed to clarify this issue. Furthermore,our study indicates that patients with vascular in-volvement have a high risk for amyloidosis, andwe believe that the administration of colchicine tothese patients may be beneficial. The routine pre-scription of colchicine to all BD patients to preventamyloidosis requires further investigation. Severaltypes of glomerular lesions can be observed in BD,and corticosteroids have been used in most of thesepatients; however, the beneficial effects of suchtreatment on the course of glomerular disease isunclear. Short-term renal prognosis is favorable inmost cases with overt glomerular disease. Amy-loidosis, GN, and renovascular involvement areclearly definable renal lesions and, in general,treatment of these lesions is more difficult than forthe involvement of other vital organs in BD.Awareness of the renal problems by physicians,especially by rheumatologists, dermatologists, andophthalmologists who are familiar with BD, maylead to a better understanding of the prevalenceand significance of renal involvement in BD.


REFERENCES1. Behcet H. Uber rezidivierende aphthose, durch ein virus

verursachte Geschwure am Mund, am Auge und an den Geni-talien. Dermatol Wochenschr 1937;105:1152-7.2. Shimizu T, Ehrlich GE, Inaba G, Hayashi K. Behçet’s

disease (Behçet’s syndrome). Semin Arthritis Rheum 1979;8:223-60.3. Kaklamani VG, Vaiopoulos G, Kaklamanis PG. Behçet’s

disease. Semin Arthritis Rheum 1998;27:197-217.4. Koc Y, Gullu I, Akpek G, Akpolat T, Kansu E, Kiraz S,

et al. Vascular involvement in Behçet’s disease. J Rheumatol1992;19:402-10.5. Akpolat T, KocY,Yeniay I, Akpek G, Gullu I, Kansu E,

et al. Familial Behçet’s disease. Eur J Med 1992;1:391-5.6. Yazici H, Yurdakul S, Hamuryudan V. Behcet’s syn-

drome. Curr Opin Rheumatol 1999;11:53-7.7. Lakhanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y,

Ohokubo T. Pathologic features of Behçet’s syndrome: A re-view of Japanese Autopsy Registry Data. Hum Pathol 1985;16:790-5.8. Akpolat T. Management of patient with Behçet’s disease.

Nephrol Dial Transplant 1998;13:3000-2.9. Zouboulis CC. Epidemiology of Adamantiades-Behçet’s

disease. Ann Med Interne 1999;150:488-98.10. Chajek T, Fainaru M. Behcet’s disease. Report of 41

cases and a review of the literature. Medicine 1975;54:179-96.11. James DG. Behcet’s syndrome. N Engl J Med 1979;301:

431-2.12. Sakane T, Takeno M, Suzuki N, Inaba G. Behcet’s

disease. N Engl J Med 1999;341:1284-91.13. Bach CD, Rubin RJ. Behcet’s syndrome. N Engl J Med

1980;302:408.14. Olsson PJ. Behcet’s syndrome. N Engl J Med 1980;302:

407-8.15. Nzerue CM. Behcet’s disease. N Engl J Med 2000;342:

587.16. Yokoyama Y, Kono T, Aoki M. Focal proliferative

glomerulonephritis with Behcet’s syndrome: report of an au-topsy case. Ryumachi 1973;13:281-8.17. Kansu E, Deglin S, Cantor RI, Burke JF Jr, Cho SY,

Cathart RT. The expanding spectrum of Behcet syndrome: Acase with renal involvement. JAMA 1977;237:1855-6.18. Hirano M, Yamagishi T, Sato M, Fueki H, Arakawa M.

A case of Behçet’s syndrome with immune complex nephritis.Naika 1978;42:511-3.19. Mace BE, Jones JG. Renal involvement in Behcet’s

disease. J R Soc Med 1978;71:74.20. Gamble CN, Wiesner KB, Shapiro RF, Boyer WJ. The

immune complex pathogenesis of glomerulonephritis and pul-monary vasculitis in Behcet’s disease. Am J Med 1979;66:1031-9.21. Williams DG, Lehner T. Renal manifestations of Beh-

cet’s syndrome. In: Behçet’s syndrome. Clinical and Immuno-logical Features, Lehner T, Barnes CG, eds. London, AcademicPress 1979;259-64.22. Olsson PJ, Gaffney E, Alexander RW, Mars DR, Fuller

TJ. Proliferative glomerulonephritis with crescent formation inBehcet’s syndrome. Arch Intern Med 1980;140:713-4.23. Beaufils H, Cassou B, Auriol M, Herreman G, Wechsler

B, Roujeau JC, et al. Kidney involvement in Behcet’s syn-

drome. A report of 11 cases studied by optic, ultrastructural andimmunopathological techniques. Virchows Arch 1980;388:187-98.24. Herreman G, Beaufils H, Godeau P, Cassou B, Wechsler

B, Boujeau J, et al. Behcet’s syndrome and renal involvement:A histological and immunofluorescent study of eleven renalbiopsies. Am J Med Sci 1982;284:10-17.25. Landwehr DM, Cooke CL, Rodriguez GE. Rapidly pro-

gressive glomerulonephritis in Behcet’s syndrome. JAMA1980;244:1709-11.26. Fukuda Y, Hayashi H. Renal involvement in Behçet’s

disease. Ensyo 1982;2:545-8.27. Wilkey D, Yocum DE, Oberley TD, Sundstrom WR,

Karl L. Budd-Chiari syndrome and renal failure in Behcetdisease. Report of a case and review of the literature. Am J Med1983;75:541-50.28. Miura M, Tomino Y, Suga T, Endoh M, Nomoto Y,

Sakai H, et al. A case of Behcet’s disease associated withmembranous nephropathy. Tokai J Exp Clin Med 1984;9:231-5.29. Sugiyama E, Suzuki H, Akagawa N, Yamashita N, Yano

S, Iida H, et al. Behcet’s disease associated with IgA nephrop-athy: Report of a case. Nippon Naika Gakkai Zasshi 1984;73:1818-1822.30. Finucane P, Doyle CT, Ferriss JB, Molloy M, Mur-

naghan D. Behcet’s syndrome with myositis and glomerulone-phritis. Br J Rheumatol 1985; 24:372-5.31. Morita H, Tanaka H, Imamura K, Kubo S, Kawamura K,

Nakayashiki H, et al. A case of vasculo-Behçet’s diseaseassociated with chronic renal failure. Saishin Igaku 1985;40:2408-16.32. Terada Y, Goto K, Ozawa K, Kijima Y, Nakayama I,

Shoji T, et al. A case of diffuse proliferative glomerulonephritisin Behcet’s disease. Saishin Igaku 1986;41:2901-6.33. Sudo J, Matsubara T, Iwai H, Ueda Y, Kameda S, Iwata

T, et al. IgA nephropathy developed in a patient with Behçet’sdisease. Kidney Dial 1987;22:893-897.34. Kuwabara K, Nakayama M, Tomita M, Ikezaki N, Itou J,

Tazoe N, et al. IgA nephropathy associated with Behçet’sdisease. Kidney Dial 1987;23:123-6.35. Furukawa T, Hisao O, Furuta S, Shigematsu H. Henoch-

Schonlein purpura with nephritis in a patient with Behcet’sdisease. Am J Kidney Dis 1989;13:497-500.36. Donnelly S, Jothy S, Barre P. Crescentic glomerulone-

phritis in Behcet’s syndrome-results of therapy and review ofthe literature. Clin Nephrol 1989;31:213-8.37. Malik GH, Sirwal IA, Pandit KA. Behcet’s syndrome

associated with minimal change glomerulonephritis and renalvein thrombosis. Nephron 1989;52:87-9.38. Akutsu Y, Itami N, Tanaka M, Kusunoki Y, Tochimaru

H, Takekoshi Y. IgA nephritis in Behcet’s disease: Case reportand review of the literature. Clin Nephrol 1990;34:52-5.39. Tietjen DP, Moore WJ. Treatment of rapidly progressive

glomerulonephritis due to Behcet’s syndrome with intravenouscyclophosphamide. Nephron 1990;55:69-73.40. Hamuryudan V, Yurdakul S, Kural AR, Ince U, Yazici

H. Diffuse proliferative glomerulonephritis in Behcet’s syn-drome. Br J Rheumatol 1991;30:63-4.

330 AKPOLAT ET AL

41. Apaydin S, Erek E, Ulku U, Hamuryudan V, Yazici H,Sariyar M. A successful renal transplantation in Behcet’s syn-drome. Ann Rheum Dis 1999;58:719.42. Numo R, Lapadula G, Covelli M, Telrizzi N. Kidney

involvement in a series of cases of Behçet’s disease. In: Beh-cet’s disease: Basic and clinical aspects, O’Duffy JD, KokmenE, eds. New York, Marcel Dekker 1991;303-8.43. Suemitsu T, Saga T, Inui A, Ariizumi M, Shogi E, Sato

H. A ciclosporin A responsive case of Behcet’s disease associ-ated with IgA nephropathy. Nippon Jinzo Gakkai Shi 1993;35:189-94.44. Yang CW, Park IS, Kim SY, Chang YS, Yoon YS, Bang

BK, et al. Antineutrophil cytoplasmic autoantibody associatedvasculitis and renal failure in Behcet disease. Nephrol DialTransplant 1993;8:871-3.45. Khan IH, Catto GR, MacLeod AM. Antineutrophil cy-

toplasmic antibody associated vasculitis and renal failure inBehcet’s disease. Nephrol Dial Transplant 1994;9:332.46. Akiyama Y, Suzuki T, Tanaka M, Ohno S, Imai F,

Kobayashi K, et al. A case of Behcet’s disease associated withaortic regurgitation and nephrotic syndrome. Ryumachi 1995;35:910-14.47. Yver L, Blanchier D, Aouragh F, Turpin Y, Chaubert N,

Laregue M, et al. Renal involvement in Behcet’s disease. Casereport and review of the literature. Nephron 1996;73:689-91.48. Hemmen T, Perez-Canto A, Distler A, Offermann G,

Braun J. IgA nephropathy in a patient with Behcet’s syndrome–Case report and review of literature. Br J Rheumatol 1997;36:696-9.49. Ben Moussa F, Turki S, Ben Taarit C, Chaabouni L,

Goucha R, Ben Maiz H. Renal involvement in Behcet’s disease.Proceedings of the 7th International Congress on Behçet’sDisease; 1996 October 10-11; Pub Adhoua, Tunis, p. 371-376.50. Ben Hmida M, Kammoun K, Kharrat M, Kaddour N,

Bahloul Z, Hachicha J, et al. Renal involvement in Behcet’sdisease. Proceedings of the 7th International Congress on Beh-cet’s Disease; 1996 October 10-11; Pub Adhoua, Tunis, p.377-379.51. Houman MH, Lamloum M, Kheder I, Boussema E,

Miled M. Behcet’s disease with glomerulonephritis and supe-rior vena cava syndrome. Proceedings of the 7th InternationalCongress on Behçet’s Disease; 1996 October 10-11; Pub Ad-houa, Tunis, p. 380-381.52. Benekli M, Haznedarogˇlu IH, Erdem Y. Glomerular

involvement in Behçet’s disease. Nephrol Dial Transplant1998;13:1351-4.53. Sakemi T, Yoshiyuki T, Ikeda Y, Suzuki N, Nagasawa

K. End-stage renal failure due to crescentic glomerulonephritisin a patient with Behcet’s syndrome. Review of the literature.Am J Nephrol 1998;18:321-4.54. Duarte M, Solans R, Gomez A, Garcia-Alfranca F,

Perez-Bocanegra C, Simeon CP, et al. Diffuse proliferativeglomerulonephritis in Behcet’s syndrome. Br J Rheumatol1998;37:466-7.55. El Ramahi KM, Al Dalaan A, Al Shaikh A, Al Meshari

K, Akhtar M. Renal involvement in Behcet’s disease: Reviewof 9 cases. J Rheumatol 1998;25:2254-60.56. Yegenaga I, Cefle A. A case of Behçet’s disease com-

plicated with nephrotic syndrome due to membranous glomer-ulonephritis. Proceedings of the XVth International Congress ofNephrology; 1999 May 2-6; Buenos Aires, Argentina, p. 43.

57. Shibata S, Miyakawa Y, Nakagawa T, Sakuta M, Naga-sawa T. Biopsy findings of the kidney in Behcet’s disease witha chronic course. Nippon Rinsho 1975;33:2381-9.58. Akpolat I, Akpolat T, Danaci M, Barıs¸ YB, Kaya N,

Kandemir B. Behçet’s disease and amyloidosis: Review of theliterature. Scand J Rheumatol 1997;26:477-9.59. Akpolat T, Akpolat I, Kandemir B. Behcet’s disease and

AA-type amyloidosis. Am J Nephrol 2000:20; 68-70.60. Utas C, Utas S, Oymak O, Keles¸timur F. Behcet’s

syndrome presenting as end-stage chronic renal failure due toamyloidosis. Nephrol Dial Transplant 1995;10:1472-3.61. Rosenthal T, Bank H, Aladjem M, David R, Gafni J.

Systemic amyloidosis in Behcet’s disease. Ann Intern Med1975;83:220-3.62. Sherf L, Griffel B, Gafni J. Amyloidosis in Behçet’s

syndrome. Proc Tel-Hashomer Hosp 1964;3:115-6.63. Beroniade V. Amyloidosis and Behcet’s disease. Ann

Intern Med 1975;83:904-5.64. Nestor G, Beroniade V, Carnaru S, Badea I. Behcet’s

disease with renal involvement (with reference to three ana-tomico-clinical cases). Rom Med Rev 1970;14:27-32.65. Hamza M, Ben Maiz H, Ayed K, Ben Ayed H. Behcet’s

syndrome with amyloidosis. Report of a case. Clinical remis-sion with colchicine. Rev Rhum Mal Osteoartic 1980;47:431-3.66. Gurler A. 250 Behçet olgusunda klinik bulgular. Lepra

Mecmuası 1980;11:156-170.67. Rubies-Prat J. Systemic amyloidosis in Behcet’s disease.

Med Clin (Barc) 1987;89:801.68. Rubies- Prat J, de la Figuera M, Obiols G, Guardia

J. Amyloidose systemique compliquant un syndrome Behçet.Nouv Presse Med 1982;11:2636.69. Skinner M. Case records of the Massachusetts General

Hospital. N Engl J Med 1982;306:1162-7.70. Strouboulis D, Stathopoulos EN, Koutsaftis FN. Ada-

mantiades-Behçet syndrome with amyloidosis. Report of a case.Proceedings of the Xth European Congress of Rheumatology;1983; Moscow, Russia, p. 1084A.71. Penza R, Brunetti L, Francioso G, Tricarico A, Lospal-

luti M. Renal amyloidosis in a child with Behcet’s syndrome.Int J Pediatr Nephrol 1983;4:35-7.72. Peces R, Riesgo I, Ortego F, Velasco J, Alvarez Grande

J. Amyloidosis in Behcet’s disease. Nephron. 1984;36:114-7.73. Sozen T, Dundar S, Oto A, Oktay A, Ariogul S. Behcet’s

disease associated with amyloidosis. Isr J Med Sci 1984;20:1071-2.74. Wechsler B, Du LTH, Hamza M, Beaufils H, Godeau P,

Chomette G. Renal and digestive amyloidosis and Behcet’sdisease. Apropos of a case. Rev Med Interne 1986;7:361-4.75. Chiba M, Inoue Y, Arakawa H, Masamune O, Ohkubo

M. Behcet’s disease associated with amyloidosis. GastroenterolJpn 1987;22:487-95.76. Cases A, Martos JA, Montoliu J, Moreno A, Revert L.

Systemic amyloidosis in Behcet’s disease. Med Clin (Barc)1987;89:250-2.77. Dilsen N, Konice M, Aral O, Erbengi T, Uysal V, Koçak

N, et al. Behçet’s disease associated with amyloidosis in Turkeyand in the world. Ann Rheum Dis 1988;47:157-63.78. Hamza M, Wechsler B, Godeau P, Hamza H, Ayed K.

Intestinal amyloidosis: an unusual complication of Behcet’sdisease. Am J Gastroenterol 1988;83:793-4.


79. Tasdemir I, Sivri B, Turgan Ç , Emri S, Yasavul U¨ ,Caglar S. The expanding spectrum of a disease: Behçet’sdisease associated with amyloidosis. Nephron 1989;52:154-7.80. Yurdakul S, Tu¨zuner N, Yurdakul I˙, Hamuryudan V,

Yazıcı H. Amyloidosis in Behçet’s syndrome. Arthritis Rheum1990;33:1586-9.81. Melikoglu M, Altiparmak MR, Fresko I, Tunc R,

Yurdakul S, Hamuryudan V, et al. A reappraisal of amyloidosisin Behcet’s syndrome. Rheumatology 2001;40:212-5.82. Bemelman FJ, Krediet RT, Schipper MEI, Arisz L.

Renal involvement in Behçet’s syndrome. Report of a case andreview of the literature. Neth J Med 1989;34:148-153.83. Werlen D, Guelpa G, Robert D. Behcet’s disease and

renal amyloidosis. Schweiz Rundsch Med Prax 1995;84:533-6.84. Simsek H, Savas C. Intestinal amyloidosis in Behcet’s

disease without renal involvement (abstr). Gastroenterology1996;110(Suppl 1):360A.85. Jimi S, Hirata M, Hayashi K. A case of Behçet’s disease

with amyloidosis. In: Studies on Behçet’s disease, Behçet’sDisease Research Committee of Japan, eds. Japan, Ministry ofWelfare 1979;122-7.86. Watanabe H, Enjoji M, Yao T. Pathomorphologic study

of simple ulcer in ileocecal region. Stomach Intestine 1979;14:749-767.87. Tanaka H. A case of Behçet’s disease associated with

systemic amyloidosis. Jpn J Nephrol 1982;14:1344-9.88. Mohammadi M, el-Idrissi F, Lachkar H, Belkhadir J,

Benabed K, Benaissa A. Association of amyloidosis and Beh-cet’s disease. Report on 2 cases. Tunis Med 1996;74:245-9.89. Filali-Ansary N, Tazi-Mezalek Z, Mohattane A, Adnaoui

M, Aouni M, Maaouni A, et al. Behcet disease. 162 cases. AnnMed Interne (Paris) 1999;150:178-88.90. Rosenthal T, Weiss P, Gafni J. Renal involvement in

Behcet’s syndrome. Arch Intern Med 1978;138:1122-4.91. Gharibdoost F, Davatchi F, Shahram F, Akbarian M,

Chams C, Chams H, et al. Clinical manifestations of Behçet’sdisease in Iran. Analysis of 2068 cases. VIth InternationalConference on Behçet’s Disease (abstract); La Revue MedecineInterne 1993:14;28S.92. Dilsen N, Konice A, Aral O, Ocal L, Inanc M, Gul A.

Risk factors for vital organ involvement in Behçet’s disease.Proceedings of the 6th International Conference on Behçet’sdisease; 1993; Amsterdam: Elsevier Science, p. 165-169.93. Mishima Y, Ishikawa K, Ueno A. Arterial involvement

in Behcet’s disease. Jpn J Surg 1973;3:52-60.94. Sueyoshi E, Sakamoto I, Hayashi N, Fukuda T, Matsu-

naga N, Hayashi K, Inoue K. Ruptured renal artery aneurysmdue to Behcet’s disease. Abdom Imaging 1996;21:166-7.95. Fukuda T, Hayashi K, Sakamoto I, Mori M. Acute renal

infarction caused by Behcet’s disease. Abdom Imaging 1995;20:264-6.96. Hamza M. Large artery involvement in Behcet’s disease.

J Rheumatol 1987;14:554-9.97. Winer-Muram HT, Headley AS, Menke P, Eltorky M.

Radiologic manifestations of thoracic vascular Behcet’s diseasein African-American men. J Thorac Imaging 1994;9:176-9.98. Sherif A, Stewart P, Mendes DM. The repetitive vascular

catastrophes of Behcet’s disease: A case report with review ofthe literature. Ann Vasc Surg 1992;6:85-9.

99. Arıogul S, Gençalp U, Keskin S, Oktay A, Oto A, So¨zenT. Behcet hastalıgˇında renal arter anevrizması. I˙stanbul Univer-sitesi Yayınları 1984;122-125.100. Han K, Siegel R, Pantuck AJ, Gazi MA, Burno DK,

Weiss RE. Behcet’s syndrome with left ventricular aneurysmand ruptured renal artery pseudoaneurysm. Urology 1999;54:162.101. Dundar S, Unal S, Sivri B, Muderrisoglu H, Kansu E,

Karacadagˇ S, et al. Behçet’s disease in Turkish population:Analysis of 200 cases. In: Recent advances in Behçet’s disease,Lehner T, Barnes CG, ed. New York, Royal Society of Medi-cine Services 1986; 219-221.102. Du LTH, Bletry O, Wechsler B, Piette JC, De Gennes

C, Kieffer E, Godeau P. Arterial manifestations in Behçet’sdisease: Fifteen cases in a series of 250 patients. In: Behçet’sdisease: Basic and clinical aspects, O’Duffy JD, Kokmen E,eds. New York, Marcel Dekker 1991;145-153.103. Assaad-Khalil SH, Rafla SM, Yacout YM, Fadel AM,

Seif MA, Hamawy RA. Prevalence of cardiovascular involve-ment in patients with Behçet’s disease using angiography, colorduplex sonography, doppler echocardiography and CATS. VII-Ith International Congress on Behçet’s Disease; 1998 October7-9; Milano, Italy; p. 187.104. Roguin A, Edoute Y, Milo S, Shtiwi S, Markiewicz W,

Reisner SA. A fatal case of Behcet’s disease associated withmultiple cardiovascular lesions. Int J Cardiol 1997;59:267-273.105. Gurler A, Boyvat A, Tursen U. Clinical manifestations

of Behcet’s disease: An analysis of 2147 patients. Yonsei MedJ 1997;38:423-7.106. Hamza M, Zribi A, Chadli A, Benayed H. Behcet’s

disease. Study of 22 cases. Nouv Presse Med 1975;4:563-6.107. Jeune R, Thivolet J, Ortonne JP, Jacquemier D. Renal

manifestations of severe human aphthous diseases. Nouv PresseMed 1980;9:2829-2831.108. Hamza M, Ben Maiz H, Ben Ayed H. Behcet’s disease

with renal manifestation. One case followed up for 6 years. SemHop 1980;56:1081-3.109. Yudis M. Nephropathy with Behçet’s syndrome. Arch

Intern Med 1979;139: 602-3.110. Yudis M, Luschinin D. Behçet’s syndrome with inter-

stitial nephritis and renal failure (abstract). Kidney Int 1978;14:668.111. Nagata K. Recurrent intracranial haemorrhage in Beh-

cet disease. J Neurol Neurosurg Psychiatry 1985;48:190-2.112. Jo SK, Yun JW, Cha DR, Cho WY, Kim HK, Won NH.

Anuric acute renal failure secondary to megalocytic interstitialnephritis in a patient with Behcet’s disease. Clin Nephrol2000;54:498-500.113. Kone-Paut I, Yurdakul S, Bahabri SA, Shafae N, Ozen

S, Ozdogan H, et al. Clinical features of Behcet’s disease inchildren: An international collaborative study of 86 cases.J Pediatr 1998;132:721-5.114. Beaufils H, de Groc F, Gubler MC, Wechsler B, Le

Hoang P, Baumelou A, et al. Hemolytic uremic syndrome inpatients with Behcet’s disease treated with cyclosporin A:Report of 2 cases. Clin Nephrol 1990;34:157-62.115. Docci D, Baldrati L, Capponcini C, Facchini F, Giudi-

cissi A, Feletti C. Hemolytic uremic syndrome/thromboticthrombocytopenic purpura in a patient with Behcet’s diseasetreated with cyclosporin. Nephron 1997;75:356-7.116. Celik I, Altundag K, Erman M, Baltali E. Cyclophos-

332 AKPOLAT ET AL

phamide-associated carcinoma of the urinary bladder in Beh-cet’s disease. Nephron 1999;81:239.117. Porru D, Pau AC, Scarpa RM, Zanolla L, Cao A, Usai

E. Behcet’s disease and the neuropathic bladder: Urodynamicfeatures: Case report and a literature review. Spinal Cord1996;34:305-7.118. Dokmeci F, Cengiz B, Ortac F. Pelvic mass in a patient

with Behcet’s disease. Obstet Gynecol 1996;87:881.119. Carswell GF. A case of Behcet’s disease involving the

bladder. Br J Urol 1976;48:199-202.120. Sakane T, Takeno M. Novel approaches to Behcet’s

disease. Expert Opin Investig Drugs 2000;9:1993-2005.121. Yazici H, Barnes CG. Practical treatment recommen-

dations for pharmacotherapy of Behcet’s syndrome. Drugs1991;42:796-804.122. International Study Group for Behçet’s disease. Criteria

for diagnosis of Behçet’s disease. Lancet 1990;335:1078-80.123. Piers A. Behcet’s disease with arterial and renal man-

ifestations. Proc R Soc Med 1977;70:540-4.124. Hyman NM, Sagar HJ. Behcet’s syndrome: Unusual

multisystem involvement and immune complexes. PostgradMed J 1980;56:182-184.125. Ota T, Takayama T. To the chronic nephritis-like dis-

ease specially to Behçet’s syndrome. Iryo 1969;23:912-6.126. Oshima Y, Shimizu T, Yokohari R, Matsumoto T,

Kano K, Kagami T, et al. Clinical studies on Behçet’s syn-drome. Ann Rheum Dis 1963;22:36-45.127. Shahram F, Davatchi F, Akbarian M, Gharibdoost F,

Nadji A, Jamshidi AR, et al. The 1996 Survey of Behçet’sdisease in Iran, study of 3153 cases. VIIth International Con-ference on Behçet’s Disease (abstract); Rev Rhum Engl Ed1996;63:538.128. Kansu E, Ozer FL, Akalin E, Guler Y, Zileli T, Tanman

E, et al. Behcet’s syndrome with obstruction of the venae cavae.A report of seven cases. QJM 1972;41:151-68.129. Zhang XOC (in Chinese). Chin J Int Med 1980;19:15-

20.130. Rigby AS, Chamberlain MA, Bhakta B. Behcet’s dis-

ease. Baillieres Clin Rheumatol 1995;9:375-95.131. Sarica K, Suzer O, Gurler A, Baltaci S, Ozdiler E,

Dincel C. Urological evaluation of Behcet patients and theeffect of colchicine on fertility. Eur Urol 1995;27:39-42.132. Zouboulis CC, Kotter I, Djawari D, Kirch W, Kohl PK,

Ochsendorf FR, et al. Epidemiological features of Adamantia-des-Behcet’s disease in Germany and in Europe. Yonsei Med J1997;38:411-22.133. Mousa AR, Marafie AA, Rifai KM, Dajani AI, Mukhtar

MM. Behcet’s disease in Kuwait, Arabia. A report of 29 casesand a review. Scand J Rheumatol. 1986;15:310-32.134. Pei-da Y, Xiuyan Y, Tan-qi L. Clinical analysis for 34

cases of Behçet’s syndrome. Clinical manifestations of Beh-cet’s disease in Iran. Analysis of 2068 cases. VIth InternationalConference on Behçet’s Disease (abstract); La Rev Med Interne1993:14;65S.135. Valesini G, Pezzi PP, Catarinelli G, Accorinti M, Priori

R. Clinical manifestations of Behçet’s disease in Italy: Study of155 patients at Rome University. In: Behçet’s disease: Basicand clinical aspects, O’Duffy JD, Kokmen E, eds. New York,Marcel Dekker 1991; 279-289.

136. Chung YM, Yeh TS, Sheu MM, Chen MS, Wen MS,Tsai HY, et al. Behcet’s disease with ocular involvement inTaiwan: A joint survey of six major ophthalmological depart-ments. J Formos Med Assoc 1990;89:413-7.137. Madanat W, Fayyad F, Zureikat H, Verity D, Narr J,

Vaughan R, et al. Analysis of 150 cases of Behçet’s diseasefrom Jordan. VIIIth International Congress on Behçet’s Dis-ease; 1998 October 7-9; Milano, Italy; p. 255.138. Nakabayashi K. Behcet’s disease and renal diseases.

Ryoikibetsu Shokogun Shirizu 1997;17:370-2.139. Vaiopoulos G, Palimeris G, Messini H, Kaklamani V,

Stamatelos G, Kaklamanis PH. Adamantiadis-Behçet’s diseasein 42 Greek patients. VIIth International Conference on Beh-cet’s Disease (abstract); Rev Rhum Engl Ed 1996;63:538.140. Pande I, Uppal SS, Kailash S, Kumar A, Malaviya AN.

Behcet’s disease in India: A clinical, immunological, immuno-genetic and outcome study. Br J Rheumatol 1995;34:825-30.141. Benamour S, Bennis R, Amraoui A. A study of 285

cases of Behçet’s disease. In: Behçet’s disease: Basic andclinical aspects. O’Duffy JD, Kokmen E, ed. New York, MarcelDekker 1991; 259-67.142. Ben Hmida M, Hachicha J, Kaddour N, Makni H,

Aydel FZ, Chakroun N, et al. ANCA in Behcet’s disease.Nephrol Dial Transplant 1997;12:2465-6.143. Chamberlain MA. Behcet’s syndrome in 32 patients in

Yorkshire. Ann Rheum Dis 1977;36:491-9.144. Assaad Khalil SH. Clinical, genetic, immunological,

and biochemical features of 180 Egyptian patient with Behçet’sdisease. In: Behçet’s disease: Basic and clinical aspects,O’Duffy JD, Kokmen E, eds. New York, Marcel Dekker 1991;269-77.145. Sanchez BJ, Grandal Y, Mendoza M, Montero R, Rejon

E, Marenco JL. Clinical characteristics, HLA antigen and mor-tality in Behcet’s syndrome in Spain. VIIIth International Con-gress on Behçet’s Disease; 1998 October 7-9; Milano, Italy; p.102.146. Calamia KT, Mazlumzadeh M, Balabanova M, Bagheri

M, O’Duffy JD. Clinical characteristics of United States pa-tients with Behçet’s disease. IXth International Conference onBehcet’s Disease (abstract). Yonsei Med J 2000:41;9S.147. Sharquie K, Al-Araji A, Al-Rawi Z, Al-Yaqubi O,

Hatem A. Behçet’s disease in Iraqi patients. A prospectivestudy from a newly established Behçet’s Disease Multidisci-pline Clinic. IXth International Conference on Behçet’s Disease(abstract). Yonsei Med J 2000:41;10S.148. Berrah A, Remache A, Ouadahi N, Ayoub S, Hakem D,

Boudjelida H, et al. Clinical manifestations of Behçet’s disease.Analysis of 58 cases. IXth International Conference on Behçet’sDisease (abstract). Yonsei Med J 2000:41;30S.149. Shukurova SM. Clinical aspects of Behçet’s disease

(BD) in patients from Tadjikistan. IXth International Confer-ence on Behçet’s Disease (abstract). Yonsei Med J 2000:41;30S.150. Berlingerio G, Tricarico G, Terlizzi N, De Cristofaro

M, Bonali C, Numo R. Behçet’s disease: report of 21 cases. In:Recent advances in Behçet’s disease, Lehner T, Barnes CG,eds. New York, Royal Society of Medicine Services 1986, p.211.151. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni


J. Colchicine in the prevention and treatment of the amyloidosisof familial Mediterranean fever. N Engl J Med 1986;314:1001-5.152. Yazici H, Bas¸aran G, Hamuryudan V, Hizli N,

Yurdakul S, Mat C, et al. The ten-year mortality in Behçet’ssyndrome. Br J Rheumatol 1996;35:139-41.153. Plotkin GR. Miscellaneous clinical manifestations, Part

I: Cardiac, vascular, renal, and pulmonary features. In: Behçet’sdisease: a contemporary synopsis, Plotkin GR, Calabro JJ,O’Duffy JD, eds. Mount Kisco, NY, Futura Publishing Com-pany 1988, pp. 203-37.154. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J,

Gross WL, et al. Nomenclature of systemic vasculitides. Pro-posal of an international consensus conference. Arthritis Rheum1994;37:187-92.155. Danaci M, Akpolat T, Koyuncu M, Unal R, Belet U.

The advantages of MRI and MRA for diagnosing Behçet’sdisease and internal jugular vein thrombosis. Comput MedImaging Graph 2000;24:121-4.156. Kingston M, Ratcliffe JR, Alltree M, Merendino KA.

Aneurysm after arterial puncture in Behcet’s disease. Br Med J1979;1:1766-7.157. Akpolat T, Danaci M, Belet U, Erkan ML, Akar H. MR

imaging and MR angiography in vascular Behcet’s disease.Magn Reson Imaging 2000;18:1089-96.158. Tuzun H, Besirli K, Sayin A, Vural FS, Hamuryudan V,

Hizli N, et al. Management of aneurysms in Behcet’s syndrome:An analysis of 24 patients. Surgery 1997;121:150-156.159. Kaklamani VG, Kaklamanis PG. Treatment of Behcet’s

disease–An update. Semin Arthritis Rheum 2001;30:299-312.160. Mojcik CF, Klippel JH. End-stage renal disease and

systemic lupus erythematosus. Am J Med 1996;101:100-7.161. Barlas S. Behcet’s disease. An insight from a vascular

surgeon’s point of view. Acta Chir Belg 1999;99:274-81.162. Yazici H, Yurdakul S, Hamuryudan V. Behcet disease.

Curr Opin Rheumatol 2001;13:18-22.163. Khayat R, Wechsler B, Bitker MO, Bletry O, Rottem-

bourg J, Luciani J, Chatelain C. Malaide de Behçet (MB) ettransplantation renale. VIth International Conference on Beh-cet’s Disease (abstract); La Rev Med Interne 1993:14;57S.

APPENDIX: Treatment and Outcome of BD-Related Glomerulonephritis (GN)

Based on Presentation of Renal Disease

Type of GN

(Reference No.) Treatment Outcome/Remarks

Silent (Insidious)

Glomerular Disease

Diffuse proliferative GN(Ig A) (38)

None Proteinuria and hematuria persistsAlive at 6 years


Colchicine 0.5 mg/d orally Renal biopsy 2 years after detection of renalproblems

Dipyridamole 2-4 mg/kg/d Improvement, decrease of serum creatinineand proteinuria

Cyclosporine 5 to 2.5mg/kg/d orally (for ocularproblems)

Alive at 3 years


None Serum creatinine increased 4 years later

Prednisolone 7.5-60 mg/dorally (after elevation ofserum creatinine)

Stabilization of serum creatinine

Alive at 10 yearsDiffuse proliferative GN(Ig A) (33)

Cepharanthin 20 mg/dorally*

No change, alive at 6 years


Methylprednisolone 24mg/d

Improvement, disappearance of proteinuria at20 days

Abbreviations: IV, intravenously; ESRD, end-stage renal disease; NSAID, nonsteroidal anti-inflammatory drug.*Cepharanthin is a biscoclaurine alkaloid used mainly in cancer models and thrombocytopenia.†Camostat mesilate is a protease inhibitor used in the management of proteinuria.‡Patient had silent (insidious) glomerular disease previously.§Acenocoumarol is an oral anticoagulant and vitamin K antagonist.

334 AKPOLAT ET AL

Type of GN


Diffuse proliferative GN(40)

Methylprednisolone IV 1 g/dfor 3 days

ESRD at 4 years, renal transplantation after14 months

Prednisolone 30 mg/d to 10mg/d orally

Azathioprine 125 mg/dAspirin 250 mg/d


NSAID ESRD at 4 years, death at 4 years due topneumonia

Mesangial proliferativeGN (55)

Prednisolone, cyclosporinelater changed toazathioprine

Stable at 24 months


Prednisolone, colchicine,warfarin

Well at 8 years without significant proteinuria

MembranoproliferativeGN (26)

Steroid, NSAID Increase of serum creatinine, hematuria, andproteinuria

Death at 5 years due to pneumonia andurinary tract infection

Focal proliferative GN(16)

Prednisolone 15-30 mg/dorally

Diagnosis at autopsy, death 4 months afterinitiation of renal problems due toperforation of intestinal ulcers

Focal proliferative GN(case 3)


No significant change at 10 months

Dipyridamole, colchicineFocal proliferative GN(Ig A) (29)

Prednisolone 10-60 mgorally every other day

Improvement, decrease of serum creatinine,proteinuria, and hematuria

Focal segmental GN(23)

Prednisolone 1 mg/kg/d to10 mg/d orally

Improvement, decrease of proteinuriaAlive at 6 months

Focal proliferative andsclerosing GN (55)

Not mentioned Alive at 1 year, serum creatinine remainednormal

Focal and segmentalglomerulosclerosis(case 4)


Colchicine

No significant change at 9 months

Minor glomerularlesion (45)

Prednisolone, cyclosporineorally

Serum creatinine was 199 �mol/L at 10 years

Methylprednisolone IV 1 g/dfor 3 days after 10 years

No change at 2 months

Prednisolone 60 mg/dorally, cyclophosphamide2.5 mg/kg/d orally

Nephrotic Syndrome



Improvement, decrease of proteinuria

Azathioprine 50 mg/d Death at 3 years due to heart failureMembranous GN (28) Prednisolone (1 month)

(1st biopsy)Anasarca before the first biopsy

Second renal biopsy 3.5 years later; at thattime proteinuria was 300 mg/d

Colchicine 1 mg/d orally(2nd biopsy)

No change at 1 week


(Continued)

Type of GN


Membranous GN (56) Prednisolone 1 mg/kg/dorally

Resolution of massive proteinuria

Minimal change GN(37)

Prednisolone � heparin No information


Prednisolone 5 mg/d orally Improvement, decrease of proteinuria

Dipyridamole 150 mg/dCamostat mesilate 1,200mg/d†

Focal proliferative GN(27)‡

Cyclophosphamide 150mg/d orally

Slow progression, increase of serumcreatinine and proteinuria


Death at 11 months due to Budd Chiarysyndrome

Acute GN/Rapidly

Progressive GN

Crescentic GN (36) Methylprednisolone IV 1 g/dfor 3 days

Improvement, decrease of serum creatinine,but proteinuria persists

Prednisolone 60 mg/d orally Alive at 20 monthsCyclophosphamide 150mg/d orally

Crescentic GN (36) Prednisolone 60 mg/d orally No change at 3 months, progression ofserum creatinine and proteinuria

Cyclophosphamide 150mg/d orally

Alive at 33 months

NoncompliantCrescentic GN (53)‡ Betamethasone 1 mg/d ESRD at 6 monthsCrescentic GN (25) Cyclophosphamide 250

mg/d, prednisolone 60mg/d orally

Death at 1 year due to sepsis

Plasma exchangeFocal proliferative andnecrotizing GN (17)

Methylprednisolone IV 80mg/d

Improvement, decrease of serum creatinineDeath at 1 month due to heart failure

Focal proliferative andnecrotizing GN (19)

No information Death due to perforation of intestinal ulcers

Focal segmentalnecrotizing GN (20)

Methylprednisolone IV 50mg/6 h for 4 days

Improvement, decrease of serum creatinineand proteinuria

Prednisolone 80 mg/d to 5mg/d orally

Alive at 19 months

Focal segmentalnecrotizing GN (Ig A)(35)

None Disappearance of proteinuria at 2 months,but hematuria persists

Patient also had Henoch-Schonlein purpuraFocal necrotizing GN(39)‡


Improvement at 60 days, ESRD at 18 months

Prednisolone 10 mg/d orallyCyclophosphamide 75 mg/dorally, thencyclophosphamide IV 0.5g/m2/mo

336 AKPOLAT ET AL

Type of GN



None Improvement, decrease of serum creatinineand proteinuria

Diffuse proliferative GN(30)‡

None Improvement, decrease of serum creatinine,proteinuria, and hematuria


Prednisolone 0.5 mg/kg/dorally

Improvement of proteinuria at 4 months

Glomerulosclerosis (44) Methylprednisolone IV 1 g/dfor 3 days

Improvement, decrease of serum creatinineon the 60th day

Focal segmental GN(51)


Improvement, decrease of serum creatinine,proteinuria, and hematuria

Prednisolone 20 mg/dorally, colchicine

Alive at 6 months

Cyclophosphamide IV 14mg/kg/mo,acenocoumarol§


Renal Beh[ccedil]et's disease: A cumulative analysis

Documents