[959] SPET ANALYSIS IN JUVENILE NEURO-BEHCET.S
Vignola, F Nobili, A Buoncompagni, G Rodriguez, G Mariani, M
Gattorno, P Picco. Genoa, Italy.
Seven children affected by Behcet disease (BD) presenting at
least one neurological sign or symptom attributable to the
underlying disorder, were studied.Three pts (n. 5-7) complained
of refractory headache, 2 (n. 3, 4) of partial epilepsy, and one
(n. 1) of intracranial hypertension (pt 1) and generalised
epilepsy (n. 2), respectively.
All pts underwent 99mTc-HMPAO high-resolution Single Photon
Emission Tomography (SPET) with the brain-dedicated gamma camera
CERASPECT (Digital Sci., USA) and an annular crystal. Images
were blindly and separately analysed by a neurophysiologist and
by a nuclear medicine specialist. Following a qualitative
analysis, areas with possibly reduced tracer uptake were
subjected to asymmetry computation by the method of Region of
Interest (ROI) drawing. ROI asymmetry was regarded as
significant when greater than 10%.Brain SPET was performed both
before and after neurological complaints ensued in pt 2, and
followed the neurological impairment in the other 6 cases.
When considering the first SPET only, one or more focal areas of
reduced tracer uptake was shown in 6/7 pts. It involved the
right caudate nucleus in pts 1 and 4 (the latter with an
abnormal EEG in right temporal region), the left thalamus in pts
3 and 7, the left hippocampal region in pts 5 and 7, and the
left caudate nucleus in pt 3. Finally, only the pt 6 with EEG
focal changes (left fronto-temporal epileptiform discharges)
displayed a reduced tracer uptake in the left frontolateral
cortex and nucleus lenticularis. In pt 1 right caudate
hypoperfusion was confirmed at the 2nd SPET when also right
temporal lobe hypoperfusion was found. In pt 2 in whom the 2nd
SPET was performed after the onset of seizures, hypoperfusion in
the right temporal lobe was found.
Concomitant MRI was performed in 5 pts. Only in 1 case (n.7) a
bilateral white matter and left cerebral peduncle
hyperintensities was disclosed.
SPET results suggest that it has a higher sensitivity than MRI
in showing brain impairment in children with BD.
ACR Poster Session D: Pediatric Rheumatology II (12:30 PM-2:00
PM)
Presentation Date: Monday, November 15, 1999, Time: 12:30PM,
Room: Hall A
[971] AN EVIDNECE FOR LINKAGE OF HLA-B LOCUS IN BEHCET'S
DISEASE BY TRANSMISSION DISEQUILIBRIUM TEST.A Gul, A H
Hajeer, S John, J Worthington, M Konice, W E Ollier, A J Silman.
Istanbul, Turkey, Manchester, United Kingdom.
background: Behcet’s disease (BD) is strongly
associated with HLA-B51 and this association has been confirmed
in different ethnic groups. However, genetic linkage of this
region has not yet been documented in BD and this might be
important in highlighting other possible areas to investigate. Aim: To ascertain whether there is a genetic linkage
between HLA-B and BD and how far such linkage extends. Patients and methods: The study group consisted of 89
individuals from 14 multicase families of BD from Turkey and 37
of them (23 male, 14 female) met the criteria of International
Study Group for the diagnosis of BD. There were 10 sib-pairs, 1
sib-trio and 3 sib-quadruples, and one of the parents was also
affected in 2 families. HLA-B and -A antigens determined by
serological methods were available in 76 individuals of 12
families. Five different polymorphic microsatellite markers,
covering the region between HLA-B and HLA-DQ (MICA5, TNFa, TNFb,
TNFd and DQCAR) were analysed by polymerase chain reaction in 89
individuals. The transmission disequilibrium test (TDT), a test
for linkage in the presence of an association, was carried out
by using the TRANSMIT programme.
Results: TDT gave a significant result for HLA-B51 (uncorrected
P<0.001, Pc<0.01) indicating an evidence for
linkage of HLA-B locus with BD. Weaker positive TDT results were
also observed for alleles of HLA-A31, MICA5-A6 and DQCAR-11 (uncorrected
P<0.05, Pc=NS). Conclusions: Although a strong association between
HLA-B51 and BD has long been known, this study showed linkage of
HLA-B locus with BD for the first time. Findings of linkage to
lesser extent in HLA-A, MICA5, DQCAR regions were compatible
with the previous studies and could be explained by the linkage
disequilibrium with HLA-B or a very close putative
susceptibility gene for BD.
Disclosure:
Keywords: Behcet's Syndrome
ACR Poster Session D: Genomics and Genetic Basis of Disease
(12:30 PM-2:00 PM)
Presentation Date: Monday, November 15, 1999, Time: 12:30PM,
Room: Hall A
[1483] PROTHROMBIN 20210A MUTATION IN BEHCET'S DISEASE.C Salvarani, L Boiardi, B Casali, I Olivieri, G Ciancio, F
Cantini, R Malatesta, F Salvi, B Mercuriali, G Rinaldi, M Govoni,
F Trotta, A Silingardi. Reggio Emilia, Italy, Potenza, Italy,
Prato, Italy, Bologna, Italy, Bologna, Italy, Reggio Emilia,
Italy, Ferrara, Italy, Reggio Emilia, Italy.
Venous and, occasionally, arterial thromboses are detected in
10-25% of patients with Behcet’s disease (BD). Thrombophilia
may have a role in the pathogenesis of thrombosis in BD.
Prothrombin 20210A mutation is an established inherited cause of
thrombophilia and its geographic distribution reveals the
highest prevalence in southern Europe, where the prevalence of
BD is higher. The aim of this study was to examine the potential
association of prothrombin 20210A allele with BD and its
clinical subgroups. 47 consecutive Northern Italian patients
with BD were recruited in 4 hospitals (Bologna, Ferrara,
Potenza, Prato, Reggio Emilia). Patients with BD fulfilled the
criteria of International Study Group for BD. The control group
consisted of 89 healthy subjects from the same geographic areas.
All patients presented with muco- cutaneous lesions including
oral ulceration (100%) and genital ulcers (55%). Positive
pathergy test was present in 13%. Eye lesions, neurological
involvement and arthritis were present in 78%, 25% and 49% of
the cases. 14 patients (30%) had deep vein thrombosis in the
legs (18 episodes) and 2 patients (4%) superficial phlebitis (3
episodes). One patient associated caval thrombosis with
Budd-Chiari syndrome. The frequency of prothrombin 20210A allele
was significantly higher in total BD patients compared to
healthy controls (14.9% versus 3.4%, p=0.01, OR: 5.0). When
compared with controls, a higher frequency of 20210A allele was
observed in the subgroup with positive pathergy test (50% versus
3.4%, p=0.003, OR 28.6), while a trend was observed in the
subgroup with thrombotic events (13.3% versus 3.4%, p=0.09, OR:
4.4). The frequency of 20210A allele was significantly higher in
patients with positive pathergy test compared with patients with
negative test (50% versus 9.8%, p=0.03, OR:9.2). 20210A
prothrombin mutation may be a contributing risk factor for
venous thrombosis in BD.
Disclosure:
Keywords: Behcet's Syndrome; Prothrombin
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1484] ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM
AND BEHCET'S DISEASE AND GIANT CELL ARTERITIS.L Boiardi,
B Casali, I Olivieri, G Ciancio, F Cantini, R Malatesta, F
Salvi, B Mercuriali, D Nicoli, E Farnetti, M Govoni, F Trotta, P
L Macchioni, C Salvarani. Reggio Emilia, Italy, Reggio Emilia,
Italy, Potenza, Italy, Prato, Italy, Bologna, Italy, Bologna,
Italy, Ferrara, Italy.
Endothelial nitric oxide (NO) inhibits the proliferation of
smooth muscle cells, protects against platelet aggregation in
vitro and in vivo and inhibits platelet and leukocyte adhesion
to endothelium. A deficit of NO production causes endothelial
dysfunction. A decreased NO production has been found in
patients with active Behcet's disease (BD). Recently, a common
polymorphism in exon 7 of the endothelial NO synthase (eNOS)
gene
(894G
T) has been reported to be a strong risk factor for coronary
artery disease. This polymorphism result in a Glu
Asp amino acid substitution. We determined whether it was
associated with BD and giant cell arteritis (GCA). 68 patients
fulfilling the criteria of International Study Group for BD, 57
patients with biopsy proven GCA and 150 healthy blood donors
were studied. All the patients and controls were genotyped by
PCR followed by RFLP.
The frequency of eNOS Asp268 alleles was significantly higher in
BD and GCA patients when compared to controls (Table). These
results suggest that Glu298Asp may be a genetic susceptibility
factor for BD and GCA.
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1485] ASSOCIATION BETWEEN THE EXTRACELLULAR MICA-9 ALLELE
AND BEHCET DISEASE (BD) IN CAUCASIANS.Z Amoura, S
Hue-Lemoine, B Wechsler, P Cacoub, S Bahram, S Caillat-Zucman, J
C Piette. Paris, France, Paris, France, Strasbourg, France.
Whether the HLA-B51 allele itself, or a closely linked gene
polymorphism is involved in susceptibility to BD is still
unclear. The MICA gene lies 40kb centromeric to HLA-B, is
transcribed in fibroblast and epithelial cell lines and may be a
candidate gene for susceptibility to BD. We have previously
reported a significant association of the MICA-A6 transmembrane
allele with BD in caucasians. However, it is unlikely that a
polymorphism in the transmembrane domain of the MICA protein
might play a role the pathogenesis of BD. We have now sequenced
exons a2-4 coding for the extracellular domains of MICA in 91
caucasians fullfilling the International Criteria for BD and 77
healthy caucasoid blood donors. Phenotype frequencies were
compared using Fisher's exact test. Although MICA-9 was the most
frequent allele in both groups, its frequency was significantly
higher in BD patients than in controls (45.05% and 27.2%
respectively, OR= 2.18 [95% Confidence interval: 1.17-4.08], p =
0.019). The distribution of the other extracellular MICA alleles
was similar in BD and control groups. Because the risk conferred
by MICA-9 was not significantly different from that conferred by
the HLA-B51 phenotype (OR= 3.18; 95% CI: 1.58-6.4),
stratification of patients and controls was done according to
HLA-B51 phenotype. Eleven out of the 13 MICA-9-positive controls
(84.6%) but only 2 out of the 64 MICA-9-negative controls (3.1%)
were B51 positive. Among the 41 MICA-9-positive BD patients, 28
(63%) were B51 positive but only 8 of 50 MICA-9-negative BD
patients (16%) were B51 positive. In conclusion, MICA-9 and B51
alleles are in strong linkage disequilibrium both in patients
and controls (p< 0.0001 by Fisher’s exact test).
Furthermore, both alleles are independently associated to BD.
Our results confirm and extend to caucasoid patients that MICA
gene polymorphism might play a role in susceptibility to BD.
However, the strong linkage disequilibrium between the MICA and
HLA-B genes makes it difficult to determine their respective
contribution to BD predisposition.
Disclosure:
Keywords: Behcet's Syndrome; MICA Gene
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1486] ASSOCIATION OF HLA-B5 WITH CLINICAL EXPRESSION AND
SEVERITY OF BEHCET’S DISEASE IN ISRAEL.I Krause, Y
Molad, A Weinberger. Petah Tikva, Israel, Tel Aviv, Israel.
Fifty-five Israeli patients with of Behcet’s disease (BD) were
included in a retrospective study to determine whether the
clinical manifestations and severity of the disease are
associated with the presence of HLA-B5. Forty-two patients
(76.4%) were Sephardic Jews, 2 (3.6%) were Ashkenazi Jews, and
11 (20.0%) were Israeli Arabs. A systemic severity score for BD
was calculated for each patient according to the potential
morbidity and mortality associated with various clinical
features as follows: 1 point for each of mild symptoms (oral
ulcers, genital ulcers, skin lesions, arthralgia, mild GI
symptoms or superficial thrombophlebitis), 2 points for each of
moderate symptoms (arthritis, anterior uveitis, deep vein
thrombosis) and 3 points for each of severe disease
manifestations (posterior or pan-uveitis, neuro-Behcet, severe
GI complications arterial lesions or major vein occlusion).
Thrombophlebitis (DVT of the legs in 4 patients, superficial
thrombophlebitis in 6 patients, 3 patients with both DVT and
superficial thrombophlebitis) was found exclusively, and in a
high percentage, in the HLA-B5 positive patients (33.3% vs. 0%,
p=0.01). The HLA-B5-positive patients also had a lower
prevalence of erythema nodosum (25.6% vs. 56.3%, p=0.03).
The rate of other mucocutaneous lesions, as well as ocular,
articular, neurological and gastrointestinal manifestations was
similar in HLA-B5-positive and negative BD patients. The
HLA-B5-positive patients, however, were significantly older at
disease onset (22.8±14.5 vs. 14.8±10.6 years, p=0.025),
and their severity score was higher (6.85±2.46 vs. 5.86±2.23,
p=0.15), though not statistically significant. The results of
the study imply that HLA-B5 in Israeli BD patients is associated
with specific clinical features of the disease and may be
associated with a tendency toward a more severe course.
Disclosure:
Keywords: Behcet's Syndrome; HLA Antigens
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1487] ASSOCIATION OF MICA POLYMORPHISM WITH HLA-B51 AND
DISEASE SEVERITY IN KOREAN PATIENTS WITH BEHCET'S DISEASE.C
S Cho, W U Kim, Y I Seo, S J Kim, T G Kim, J W Mok, K S Park, J
K Min, Y S Hong, S H Lee, S H Park, H Y Kim. Seoul, Korea,
Republic of Korea.
MHC class I chain-related gene A (MICA) has been recently
associated with Behcet's dissease (BD). To investigate the
association of MICA with Korean BD, we studied MICA polymorphism
in 82 BD patients and 204 healthy controls (HC) and compared it
to the presense of HLA-B51 and clinical manifestations of BD.
Triplet repeat polymorphism, (GCT/AGC)n, within the
transmembrane of MICA was determined by PCR-SSCP. Genotype
analysis showed that patients with BD had a higher frequency of
MICA6 and a lower frequency of MICA5.1 compared to HC (A6: 50.0%
vs. 26.5%, relative risk [RR]=2.78, A5.1; 3.7% vs. 19.1%, RR=0.161).
Comparison of phenotypes showed higher frequencies of MICA6 (RR=2.48),
HLA B51 (RR=2.01) and MICA6 (+)/B51(+) (all positive of MICA6
and B51; RR=1.89) in BD patients. In contrast, patients with BD
had lower MICA4 (RR=0.01) and 5.1 (RR=0.01). The frequency of
MICA6 (-)/ B51 (+) was not different between BD patients and HC.
MICA6 in BD as well as HC was positively associated with HLA-B51
(BD: p<0.001, HC: P<0.001) but negatively associated with
MICA4 (BD: p<0.001, HC: p=0.003), MICA5.1 (BD: p=0.003, HC:
p=0.001) and MICA9 (BD: p=0.004, HC: p<0.001). Among theses
associations, MICA6 homozygote showed highest corespondence to
susceptibility of BD (RR 6.1 [95% CI: 3.1-12.0]). Patients with
MICA 6 tended to have more intestinal involvement (p=0.07),
whereas patients (n=18) with MICA9 had less severe complications
of BD in terms of uveitis, thrombosis, intestinal and neurologic
involovement than those (n=64) without (p=0.008). However,
associations of HLA B51 with any clinical features were not
found. Collectively, MICA6 homozygote rather than HLA-B51 was
strognly associated with Korean BD. MICA6 was tightly linked to
HLA-B51 but inversely related to non-MICA 6 genes. The clinical
features of BD were presented differently according to MICA
subtypes. Our results suggest that MICA polymorphism could play
an important role in determining susceptibility and severity of
BD.
Disclosure: Supported a grant by The Catholic University
of Korea
Keywords: Behcet's Syndrome; HLA Typing
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1488] CHANGES IN LYMPHOCYTE SUBSETS WITH MICROBIAL AND
AUTO-IMMUNE ANTIGENS IN BEHCET'S DISEASE.A Kibaroglu, E
Eksioglu-Demiralp, H Direskeneli, T Akoglu. Istanbul, Turkey.
Various microorganisms such as streptoccocia and auto-immune
antigens cross-reactive with microbial homologues such as 60 kD
heat-shock protein (HSP60) were previously implicated in the
etiopathogenesis of Behcet's disease (BD).
In this study, peripheral blood mononuclear cells from patients
with BD (n:16) and healthy controls (n:11) were cultured with
protein extracts of S. Sanguis KTH-1 (SS), E.Coli (EC),
lipopolysaccharide (LPS) and mixed BD-related HSP60 peptides (residues
136-50, 179-97, 244-58 and 336-51) for five days. The changes in
T cell (CD4+abTCR+, CD4+gdTCR+,
CD8+abTCR+, CD8+gdTCR+,
CD4+CD16+, CD4+CD56+ and CD11b+) and NK subsets (CD16+CD56+)
were determined with flow cytometry.
In unstimulated cultures, gdTCR+,
CD4+gdTCR+, CD8+gdTCR+,
CD8+abTCR+, CD4+CD56+ and CD8+CD11b+
cells were increased in BD compared to healthy controls. In
antigen-stimulated cultures of BD patients, CD3+ and abTCR+
T cells were increased with HSP60 peptides whereas CD16+CD56+ NK
cells were increased after EC and LPS. In the healthy control
group, in addition to abTCR+ T cells,
CD4+ and CD4+CD56+ T cells responded to HSP60 peptides and
CD8+CD11b+, CD56+ and CD4+CD56+ cells responded to SS and EC.
Significant increases in unstimulated T cell subsets may suggest
the presence of an in vivo T cell activation in BD. In both
patients and controls, different patterns of responses were
observed against bacterial extracts compared to HSP60 peptides
suggesting that whole bacteria and purified antigens may
activate different lymphocyte subsets with a possible
superantigen-like common effect of whole bacteria extracts.
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1489] ELEVATED SOLUBLE FAS IN PATIENTS WITH BEHCET'S
UVEITIS: CORRELATION WITH UVEITIS SEVERITY.W U Kim, S J
Kim, M H Kim, J S Yoo, T W Han, S M Chung, J K Min, Y S Hong, S
H Lee, S H Park, C S Cho, H Y Kim. Seoul, Republic of Korea.
Fas mediated apoptosis is known to play an important role for
the maintenance of immune privilege of eye. To assess the
possibility that a defective apoptosis might be involived in the
pathogenesis of Behcet's uveitis (BU), soluble Fas (sFas), which
inhibits Fas mediated apoptosis, and soluble Fas ligand (sFasL)
were measured in paired sera and aqueous humor from patients
with Behcet's uveitis (n=22), those with non-Behcet's uveitis (NBU,
n=17) and age, sex matched non-uveitis controls (NUC, n=24) by
ELISA. The severity of uveitis was determined by Hogan's grading
system (04 grade) at the time of sampling. Levels of sFas in
aqueous humor were significantly higher in patients with BU (median
[range] 264 [18,1870] pg/ml) or NBU (302 [210,630] pg/ml)
compared to those with NUC (216 [0,420] pg/ml) (p=0.01 and
p=0.003, respectively). Aqueous sFas correlated well with serum
sFas in BU (r=0.578, p=0.01), but not in NBU and NUC. In contrat,
serum sFasL was significantly decreased in BU compared to NUC
(43 [0,90] v.s. 55 [0,90] pg/ml, p=0.03). Patient's with severe
BU (grade 2,
n=14) had a higher median level of sFas in both sera and aqueous
humor and had a lower median level of aqueous sFasL compared to
those with mild BU (grade <2, n=8) (serum sFas: 438 v.s. 373
pg/ml, p <0.05, aqueous sFas: 346 v.s. 220 pg/ml, p=0.01,
aqueous sFasL: 15 v.s. 62 pg/ml, p=0.038). Aqueous sFas was also
higher in severe NBU (p=0.02), but serum sFas was not different
between severe and mild NBU. Three months after treatment,
aqueous sFas (n=11) was significantly decreased along with
improvement of BU (pre-treatment 423 [18,1870], post-treatment
243 [9,360] pg/ml, p=0.003). Conclusively, sFas was elevated and
sFasL was decreased in BU, especially in severe disease. Our
data suggest that ineffective Fas mediated apoptosis of
infiltrating inflammtory cells may result in a loss of immune
privilege and a progression of uveitis. Serum and aqueous sFas
could be useful to assess the severity of BU.
Disclosure: Supported by grants from the Catholic
Research Institutes of Medical Science
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1490] CLONAL PROLIFERATION OF B CELL BEARING
IMMUNOGLOBULIN g HEAVY CHAIN IN THE
SYNOVIUM OF BEHCET'S DISEASE WITH ARTHRITIS.C H Suh, C H
Song, J Song, Y B Park, W K Lee, C H Lee, S K Lee, D S Bang.
Seoul, Republic of Korea, Seoul, Republic of Korea.
Objective. We previously found the evidence of the clonal
proliferation of B cell bearing immunoglobulin (Ig) m
heavy chain in the synovium of a Behcet's disease (BD) patient
with arthritis. To define the role of B cell with Ig g
heavy chain in the pathogenesis of arthritis in Behcet's disease,
we examine the Ig g heavy chain
repertoire expressed in synovial tissue. Methods. We generated cDNA from peripheral blood
lymphocyte (PBL) and synovial tissue of a Behcet's disease
patient with arthritis and PBL of age- and sex-matched control.
PCR based complementarity determining region3 (CDR3) finger
printing assay was performed and subsequently cloning and
sequencing of restricted CDR3 domain were done. After synthesis
of CDR3 probe, Ig g heavy chain
variable region sequence was searched with colony hybridization
method. Results. The PBL of control showed no restricted band of
CDR3 length on PAGE except VH4 family,
but the PBL of BD expressed the restriction of CDR3 length in VH3,
VH4, VH5 and
VH6 family. In the synovial tissue of
BD, restricted CDR3 length was seen in all heavy chain family
except VH4. Among them, dominant
restricted band was seen in 15 amino acid length CDR3 domain of
VH3 family in the synovial tissue.
After sequencing of this domain, 24-mer probe was synthesized;
5'-GCTCGGGGAGTTACCCCTGATGCT-3'. Seven positive colonies were
detected from 50 colonies with this probe. Among them, four
colonies had nearly identical Ig variable region nucleotide
sequence. The variable region sequence is produced from germline
V3-30, DXP'1, and JH3
gene segment. There are numerous somatic mutations in the
variable region and predominant replacement mutations in the CDR. Conclusion. These data suggest that there is
antigen-driven clonal proliferation of B cell bearing Ig g
heavy chain in the synovium of BD patient with arthritis.
Disclosure: Ministry of Health and Welfare of the
Republic of Korea(1997) HMP-97-M-2-0041
Keywords: Behcet's Syndrome; B Cells
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1491] A REAPPRAISAL OF AMYLOIDOSIS IN BEHCET'S SYNDROME.M Melikoglu, M R Altiparmak, I Fresko, S Yurdakul, V
Hamuryudan, H Yazici. Istanbul, Turkey.
Purpose: Behcet's syndrome ( BS ) is a multi-systemic vasculitis
with protean manifestations. It is characterized by a heightened
state of inflammation and there have been various reports that
associate the syndrome with secondary amyloidosis. We aimed to
evaluate the clinical features and outcome of the patients with
BS and amyloidosis and to analyze the risk factors related to
the development of amyloidosis.
Method: A retrospective chart review was done to determine the
frequency of amyloidosis in the patients with BS among the
registered 3500 patients between 1977-1999.The data from 14
patients with amyloidosis were compared with the data obtained
from 718 patients without amyloidosis who were followed for at
least 3 years between 1988- 1993. Multiple stepwise logistic
regression analysis was used to determine the risk factors for
the development of amyloidosis .
Results: All of the 14 patients with amyloidosis, (F/M:2/12,
mean age at the diagnosis of BS: 27 years ( range 22-41 ) )
presented with the nephrotic syndrome or significant proteinuria.
The mean time to the onset of amyloidosis after the onset of BS
was 8.1 years ( range 3-15 ). The mean duration of follow up
after amyloidosis was 3.4 years ( range 1-11). Seven out of 14
were alive at the time of the evaluation. Six of them have
normal renal function and one is undergoing hemodialysis.Six
patients died and one was lost to follow up.The most significant
clinical association with the development of amyloidosis was
peripheral and pulmonary arterial involvement and arthritis( p
< 0.05 ).
Conclusion: Amyloidosis in BS is rather rare and carries a 50-60
% mortality at 3.4 ( range 1-11 ) years. Certain disease
manifestations, most significantly peripheral and pulmonary
arterial involvement and arthritis were essential for the
development of amyloidosis.
Disclosure:
Keywords: Amyloidosis; Vasculitis
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1492] CLINICAL AND IMMUNOLOGIC RESPONSE TO INTERFERON
THERAPY IN PATIENTS WITH BEHCET'S DISEASE.S Haznedaroglu,
A Kosar, Y Karaaslan, B Goker, Y Buyukasik, O Ozcebe, I
Haznedaroglu, S Kirazli, S Dundar. Ankara, Turkey, Ankara,
Turkey.
Behcet's Disease (BD) is a multisystem vasculitic disorder
characterized by a strong geographical predilection. Its
clinical spectrum ranges from recurrent mucosal ulcers to
devastating major vascular involvement. In the countries where
it is prevalent, BD constitutes an important cause of morbidity
and a frequent reason for hospital visits. Etiology of BD is
unclear, and even though environmental and genetic factors have
been suggested to play a role, immunologic dysfunction remains
to be the cornerstone in its pathogenesis. We studied the
effects of interferon-alpha-2a (IFN) therapy on tumor necrosis
factor-alpha (TNF-alpha), TNF-alpha2-receptor (TNF-alpha2R),
interleukin-2 (IL-2), IL-2 receptor (IL-2R) and E-selectin
concentrations, as well as clinical response in patients with
active BD. Twenty-two patients (7M, 15F) with active BD were
studied. All patients fulfilled the criteria of International
Study Group for BD. Mean age at study entry was 34 (range 20-52)
years. Oral aphtae, genital aphtae, papulopustular skin lesions,
uveitis, arthritis, deep venous thrombosis and erythema nodosum
were present at diagnosis in 22,11, 8,6,5,4 and 3 patients. IFN,
3 million units subcutaneously (Roferon-A, Roche) was given
twice weekly for 90 days. Fifteen healthy control samples, as
well as baseline and post treatment serum from study patients
were stored at -30°C until assayed
by sandwich-type enzyme immunoassays. Twenty of the 22 patients
had clinical improvement during the study period. Median
baseline E-selectin, TNF-alpha and TNF-alpha-2R levels were
elevated compared to controls. There was a significant decrease
in these markers in response to IFN therapy. However, baseline
IL-2 and IL-2R levels did not differ from controls, and there
was no significant change after therapy. These results confirm
the efficacy of IFN therapy in patients with BD and suggests the
role of TNF-alpha, TNF-alpha2R and E-selectin in its
pathogenesis.
Disclosure: This study was supported, in part, by Roche
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1493] PULSE CYCLOPHOSPHAMIDE (PCP) FOR OCULAR LESIONS OF
BEHCET'S DISEASE: DOUBLE BLIND CROSSOVER STUDY.F
Davatchi, F Shahram, H Chams, M Akbarian. Tehran, Iran.
INTRODUCTION: Ocular lesions of Behcet's Disease
(BD) need aggressive treatment to prevent from severe loss of
vision or blindness. Although cytotoxic drugs are thought to be
the main therapeutic arsenal, no control study has yet been done
to demonstrate their efficacy. This study was designed to
evaluate the short-term efficacy of pulse cyclophosphamide in a
randomized double blind control study. MATERIALS & METHODS: PCP was used as 1g per
square meter of body surface in 1 liter normal saline by
intravenous infusion, once monthly for the PCP group. Normal
saline was administered alone for the placebo group.
Prednisolone was given to both groups as 0.5 mg/kg/ daily. After
3 months (3 PCP), the two groups were interchanged. Inclusion
Criteria were: 1- Fulfilling the Iran criteria for BD.
2- Existence of active posterior uveitis (PU) and/or retinal
vasculitis (RV). A Disease Activity Index (DAI)
was calculated for each patient and for each section of each eye
(anterior chamber, uvea, and retina) upon their inflammatory
state. Visual acuity (VA) was calculated by the
Snellen chart. RESULTS: The mean VA improved from 3.7 to 4.9 (t
=3.309, p<0.002) for the PCP group and from 4.4 to 4.5 (t=
0.317, p=0.75) for the placebo group. The difference between the
two groups was significant (t =2.402, p<0.02). The mean DAI
for AU improved from 1.2 to 0.4 (t = 3.273, p<0.003) for the
PCP group and from 1.2 to 0.7 (t= 1.972, p=0.057) for the
placebo group. However, the difference between the two groups
was not significant (t= 0.595, p=0.55). The mean DAI for PU
improved from 2.2 to 1.8 (t=1.898, p=0.063) for the PCP group
and from 2.1 to 1.8 (t= 1.27, p=0.21) for the placebo group. The
difference between the two groups was not significant (t=0.495,
p=0.62). The mean DAI for RV didn't change (DAI=1.2, t= 0.127,
p=0.9) for the PCP group while it aggravated from 0.9 to 1.1 (t=
1.27, p=0.21) for the placebo group. The difference between the
two groups was not significant (t=0.507, p=0.61). CONCLUSION: VA improved in the PCP group but not
in the placebo group demonstrating the efficacy of PCP and
steroids together, but not steroids alone (statistical
significance). The difference was not significant for
inflammatory indexes because they may improve with steroids
alone for a short time.
Disclosure:
Keywords: Behcet's Syndrome; Cyclophosphamide
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1494] THE EFFECT OF LOW DOSE INTRADERMAL INTERFERON ALPHA
ON PATHERGY REACTION IN BEHCET'S DISEASE.A Oguz, S
Erdogan, C Mat, H Yazici. Izmit, Turkey, Istanbul, Turkey,
Istanbul, Turkey, Istanbul, Turkey.
Interferon alpha (INFa) causes immunopathologic changes in the
skin when injected intradermally [1]. On the other hand systemic
INFa may induce the pathergy reaction in Behcet's disease (BD)
[2]. We investigated the effects of low dose intradermal INFa on
the pathergy reaction in patients with BD.
Methods: We studied 30 pathergy positive patients with BD,
divided into groups A, B and C. Group C patients were also PPD
positive and there were 10 patients in each group. 10 healthy
controls (HC), group D, none of whom were pathergy positive,
were also studied. Groups A, C and D received INFa-2a 500.000U
intradermally 3 times a week for 5 times into one forearm and
group B received saline instead of INFa. The pathergy tests
(piercing the epidermis and the dermis with a needle) were
applied to an area in the immediate vicinity of the INFa or
saline injections and to the opposite forearm before and 48
hours after the last INFa or saline injection in all groups
except for group C among whom PPD tests were done in the same
manner.
Results: In group A, pathergy reactions became negative after
INFa injections in 7/10 patients. Group B patients remained
pathergy positive. INFa had no effect on the PPD test among
group C and did not induce the pathergy reaction among the HC,
group D.
Conclusion: Intradermal INFa2a, contrary to its reported
systemic effect, diminishes the pathergy reaction in BD.
References:
[1]: Tong Y, Tucker SB. Am J Med Sci 1993,306:1;23-7
[2]: Budak-Alpdogan T, et al. Br J Rheumatol 1998, 37:11; 1148-5
Disclosure:
Keywords: Behcet's Syndrome; Interferon-alpha
ACR Poster Session E: Vasculitis II (8:00 AM-9:30 AM)
Presentation Date: Tuesday, November 16, 1999, Time: 8:00AM,
Room: Hall C
[1495] THE PREVALENCE OF LOWER INTESTINAL INVOLVEMENT IN
BEHCET'S DISEASE.Y M Kang, G W Kim, H IK Bae. Taegu,
Republic of Korea, Taegu, Republic of Korea.
Objective: To analyze the frequency of lower intestinal
involvement and their pathologic findings in patients with
Behcet's disease(BD). Methods: We performed colonoscopic examinations in 46
consecutive patients with BD and 27 patients with rheumatoid
arthritis(RA) as controls. Mucosal tissue biopsy specimens were
obtained from the ulcers and nonlesional mucosa of some patients
with BD and RA. Results: Abnormal findings of colonoscopic examination,
such as aphthous ulcers, polyps, hyperemic mucosa and lymphoid
hyperplasia, were present in 41.3% of BD patients(25.9% in RA
patients, p=0.185). Aphthous ulcers in terminal ileum and colon
were significantly more common in BD patients(26.1% vs. 3.7% in
RA patients, p=0.024) and were distributed in terminal
ileum(78.6%), cecum(14.3%) and sigmoid colon(7.1%) but polyps
were more common in RA patients(22.2% vs. 6.5% in BD patients,
p=0.068). In BD patients, neutrophilic infiltrations around
ulcers were significantly more severe in terminal ileum(p=0.005)
and colon(p=0.036) compared with those of nonlesional mucosal
tissues, and plasma cell infiltration in ulcers was more severe
than that in nonlesional mucosa of terminal ileum(p=0.002) but
not of colon(p=0.389). Infiltrations of eosinophils and
lymphocytes were not significantly different between ulcers and
nonlesional mucosa in BD patients. Infiltrations of inflammatory
cells in nonlesional mucosal tissues were not significantly
different between BD and RA patients. Conclusion: The frequency of lower intestinal involvement
in BD was 41.3% on colonoscopic examination of which aphthous
ulcers were most common and the microscopic findings around
ulcers showed that infiltrations of neutrophils and plasma cells
were more severe than those of nonlesional mucosa in terminal
ileum.
T) has been reported to be a strong risk factor for coronary
artery disease. This polymorphism result in a Glu 
2,
n=14) had a higher median level of sFas in both sera and aqueous
humor and had a lower median level of aqueous sFasL compared to
those with mild BU (grade <2, n=8) (serum sFas: 438 v.s. 373
pg/ml, p <0.05, aqueous sFas: 346 v.s. 220 pg/ml, p=0.01,
aqueous sFasL: 15 v.s. 62 pg/ml, p=0.038). Aqueous sFas was also
higher in severe NBU (p=0.02), but serum sFas was not different
between severe and mild NBU. Three months after treatment,
aqueous sFas (n=11) was significantly decreased along with
improvement of BU (pre-treatment 423 [18,1870], post-treatment
243 [9,360] pg/ml, p=0.003). Conclusively, sFas was elevated and
sFasL was decreased in BU, especially in severe disease. Our
data suggest that ineffective Fas mediated apoptosis of
infiltrating inflammtory cells may result in a loss of immune
privilege and a progression of uveitis. Serum and aqueous sFas
could be useful to assess the severity of BU.