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Antiphosphatidylserine-Prothrombin Complex Antibodies in 3 Patients With Behçet Disease Involving Superficial Vein Thrombophlebitis FREE

Tamihiro Kawakami, MD, PhD; Masahide Yamazaki, MD, PhD; Masako Mizoguchi, MD, PhD; Yoshinao Soma, MD, PhD
[+] Author Affiliations

Author Affiliations: Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan (Drs Kawakami, Mizoguchi, and Soma); and Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan (Dr Yamazaki).


Arch Dermatol. 2009;145(2):171-175. doi:10.1001/archdermatol.2008.570.
Text Size: A A A
Published online

ABSTRACT

Background  Superficial vein thrombophlebitis is the common vascular symptom in Behçet disease and is characterized as erythema nodosum–like eruptions. Some studies have reported the presence of antiphospholipid antibodies (Abs) in patients with Behçet disease.

Observations  We measured lupus anticoagulant, anticardiolipin, anti–β2-glycoprotein I, and antiphosphatidylserine-prothrombin complex antibody (Ab) levels in 3 patients with Behçet disease involving superficial vein thrombophlebitis. High levels of IgM antiphosphatidylserine-prothrombin complex Abs were found (mean [SD], 50.3 [43.1] U/mL; normal, <10 U/mL). One of the patients with Behçet disease was positive for both IgM and IgG antiphosphatidylserine-prothrombin complex Abs, and 2 were positive for lupus anticoagulant. Two patients were also positive for IgM anticardiolipin Abs, but the titers were low. In contrast, none of the patients with Behçet disease was positive for IgG anticardiolipin Abs or IgG or IgM anti–β2-glycoprotein I Abs.

Conclusions  A high titer of IgM antiphosphatidylserine-prothrombin complex Abs was found in our patients with Behçet disease involving superficial vein thrombophlebitis. We speculate that there is a relationship between the antiphospholipid Abs, especially IgM antiphosphatidylserine-prothrombin complex Abs, and superficial vein thrombophlebitis complications in Behçet disease. This study suggests that elevated serum antiphosphatidylserine-prothrombin complex Ab levels might play some role in the development of the vascular manifestations in Behçet disease.

Figures in this Article

Behçet disease (BD) is a multisystem, inflammatory disorder characterized by recurrent oral aphthous ulcers and at least 2 of the following features: recurrent genital ulcers, eye lesions, skin lesions, and a positive pathergy test result. Some authors suggest that the common histopathological lesion in all organ systems of the patient with BD is vasculitis.1,2 It is believed that much of the pathologic process in BD may be secondary to vasculitis.3 Vessel lesions of various sizes, such as small-vessel vasculitis and large venous or arterial lesions, can be involved, and venous lesions are a characteristic manifestation of the disease.4,5 The common cutaneous manifestations were characterized as erythema nodosum–like eruptions, a pustular pathergic tissue reaction to needle trauma, oral and genital ulceration, and acneiform folliculitis. Microscopic examination of the erythema nodosum–like lesions in the lower extremities reveals superficial vein thrombophlebitis (SVT) in the deep dermis to subcutaneous fat and small-vessel vasculitis involving, in particular, the venules, with perivascular neutrophilic and lymphocytic infiltrations in the vessel walls. The cutaneous vasculitis in BD is predominantly venulitis or thrombophlebitis with relative sparing of the arterial compartment.3 Superficial vein thrombophlebitis tends to be the common cutaneous vascular symptom in BD, although the mechanism is unknown.

Lupus anticoagulant (LAC) activity detected by a phospholipid-dependent coagulation assay is heterogeneous with respect to the specificities and functional capacities of the antibodies (Abs).6 Detection of LAC activity requires a careful sequential series of steps. Despite internationally accepted guidelines and many efforts to improve the standardization of LAC assays, it is very difficult to standardize the laboratory diagnosis of LAC.7 Detection of antiphospholipid cofactor Abs in addition to the classic anticardiolipin (aCL) Abs and LAC seems to be of considerable clinical importance. Atsumi et al8 and Amengual et al9 suggested that antiphosphatidylserine-prothrombin complex (aPS/PT) Abs, rather than antiprothrombin Abs alone, are associated with symptoms of LAC activity. Some studies have reported the presence of antiphospholipid (aPL) Abs in patients with BD.10,11 Other reports have indicated that erythema nodosum–like lesions with BD in the lower extremities resemble cutaneous polyarteritis nodosa.12,13 We previously reported a high titer of aPS/PT Abs in patients with cutaneous polyarteritis nodosa.14

In this study, we investigated LAC and levels of aCL Abs, aPS/PT Abs, and anti–β2-glycoprotein I (aβ2GPI) Abs in the serum of the 3 patients with BD involving SVT. To our knowledge, serum levels of aPS/PT Abs in patients with BD have not been previously investigated.

REPORT OF CASES

CASE 1

A 32-year-old Japanese man presented with recurrent fever, erythema nodosum–like lesions, and orogenital ulcerations. He had a 6-year history of recurrent oral aphthous ulcers and acneiform lesions. The patient complained of recent arthralgia of his ankles and knees, as well as myalgias on both his legs. A physical examination revealed erythematous macules on his lower extremities, several ulcers in the oral cavity, and ulcers on the right scrotum (Figure 1A). The results of a pathergy test were positive. A biopsy specimen of the macules showed medium-sized vessel vasculitis and thrombi with a mild to moderate inflammatory cell infiltrate in the septa and lobules of the subcutaneous adipose tissue (Figure 1B).

Place holder to copy figure label and caption
Figure 1.

Findings from physical examination and histopathological analysis for patient 1. A, Lower extremities showing erythema nodosum–like lesions. B, A lesional skin biopsy specimen of the erythematous macules on the right leg shows typical superficial vein thrombophlebitis in the subcutaneous fat (hematoxylin-eosin, original magnification ×20).

Graphic Jump Location
CASE 2

A 28-year-old Japanese man with a 4-week history of fever was admitted to our hospital. The patient reported having skin eruptions, myalgias, and arthralgias on his lower extremities for approximately 3 weeks. The results of a pathergy test were positive. Physical examination revealed erythematous macules scattered over his legs (Figure 2A). Histopathological analysis revealed a medium-sized, thrombosed blood vessel with moderate cell infiltration and panniculitis in the dermis to subcutaneous fat (Figure 2B). Elastic–van Gieson staining revealed local irregular internal elastic lamina in the thick-walled vessels (Figure 2C).

Place holder to copy figure label and caption
Figure 2.

Findings from physical examination and histopathological analysis for patient 2. A, Erythematous eruption with painful erythematous macules over the right extremities. B, A lesional skin specimen from the leg shows superficial vein thrombophlebitis in the middle to deep dermis (hematoxylin-eosin, original magnification ×40). C, Elastic–van Gieson staining reveals local irregular elastic fibers in the blood vessel wall (original magnification ×100).

Graphic Jump Location
CASE 3

A 53-year-old Japanese woman with a 1-month history of recurrent, tender nodules on her lower extremities and of recurrent aphthous ulcers of her oral mucosa, and genital ulcers was referred to our clinic. She has been thrombocytopenic for several years and had had a late miscarriage. Physical examination revealed multiple erythema nodosum–like lesions and livedo reticularis over both thighs and legs (Figure 3A). In addition, she had begun to experience arthralgias and myalgias, with cutaneous eruptions on her legs and feet. Pathergy test results were positive. A skin biopsy specimen obtained from the erythema of her right lower extremity demonstrated SVT in the subcutaneous fat (Figure 3B). There was an inner elastic lamina confirming that the blood vessel was a vein (Figure 3C).

Place holder to copy figure label and caption
Figure 3.

Findings from physical examination and histopathological analysis for patient 3. A, Erythematous macules and livedo reticularis on right knee. B, Microscopic examination of a specimen from her right lower extremity reveals superficial vein thrombophlebitis with moderate neutrophils and mononuclear cell infiltrations in the dermis and in the septa and lobules of the subcutaneous fat (hematoxylin-eosin, original magnification ×20). C, Elastic–van Gieson staining reveals degenerated elastic fibers in the blood vessel wall (original magnification ×100).

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LABORATORY FINDINGS

The following blood tests in all 3 patients were within the normal range or negative: thyroid function; liver function; cryoglobulins; complement fractions C3/C4/CH50; antinuclear Abs; anti-DNA, anti-SSA, anti-SSB, anti-RNP, and anti-Sm antineutrophil cytoplasmic Abs; serological tests for hepatitis B and C, human cytomegalovirus, human immunodeficiency virus, and Epstein-Barr virus; prostatic-specific antigen; and carcino-embryonic antigen. None of the patients demonstrated any abnormal evidence of prothrombin time, partial thromboplastin time, protein S and protein C activity, antithrombin III, factor V Leiden (resistance to activated factor V), prothrombin gene mutation (G20210A), and homocysteine.

METHODS

The diagnoses in the 3 patients with BD were made according to criteria proposed by the International Study Group for BD.15 Each patient presented with erythema nodosum–like lesions on their lower extremities. We found SVT in all 3 patients, based on the presence of cutaneous lesions in their skin biopsy specimens. The 3 patients did not have any other vascular involvement including arterial and venous thrombosis. All plasma and serum samples were collected and immediately centrifuged at 3000 rpm for 30 minutes at 4°C. After filtration, aliquots of platelet-free plasma were stored at −70°C until used for the LAC clotting tests. According to guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibody, LAC was screened by measuring diluted Russell viper venom time and kaolin clotting time and was confirmed by mixing studies and demonstration of phospholipid dependence.16 IgG and IgM (IgG/IgM) aPS/PT Abs and IgG/IgM aCL Abs were measured using a specific enzyme-linked immunosorbent assay (ELISA) (Medical & Biological Laboratories, Nagoya, Japan), according to the manufacturer's protocols. IgG and IgM aβ2GPI Abs were determined according to a standardized aβ2GPI Ab ELISA (Diagnostica Stago, Asnières, France). The cutoff values for IgG/IgM aPS/PT Abs, IgG/IgM aCL Abs, and IgG/IgM aβ2GPI/CL Abs were set at 12 U/mL and 10 U/mL; 10 U/mL and 10 U/mL; and 10 U/mL and 10 U/mL, respectively. All data are expressed as means and standard deviations.

The experimental protocol was approved by the St Marianna University ethics committee, and informed consent was obtained from all patients.

RESULTS

High titers of serum IgM aPS/PT in the patients with BD (50.3 [43.1] U/mL) were detected (Table). One of the patients with BD (case 1) was positive for both IgM and IgG aPS/PT Abs. Two patients (cases 2 and 3) were positive for LAC. Two of the 3 patients with BD were positive for IgM aCL Abs, but the titers (13 U/mL and 11 U/mL) were relatively low. None of the patients was positive for IgG aCL Abs or IgG/IgM aβ2GPI Abs.

Table Graphic Jump LocationTable.  Lupus Anticoagulant (LAC) and Antiphospholipid Antibodies in 3 Patients With Behçet Disease Involving Superficial Vein Thrombophlebitis

COMMENT

The 3 patients with BD in our study showed skin biopsy–proven SVT in their erythema nodosum–like lesions, and we detected high titers of IgM aPS/PT Abs in their serum samples. In contrast, while we detected IgM aCL Abs in 2 of our patients, the titer was not high. Zouboulis et al17 reported high IgM aCL Ab titers in patients with both BD and erythema nodosum. We detected LAC in the 2 patients who had erythema nodosum–like eruptions. Mader et al18 reported that their patients with BD were not positive for LAC. Ethnic and geographical differences in BD related to the clinical manifestations are well known,19 and LAC and aCL Abs might be influenced by those factors. In the present study, we speculate on the relationships between the presence of aPL Abs, especially IgM aPS/PT Abs, and the SVT complication in BD. We propose that serum aPS/PT Abs could have an important role as biomarkers of disease and should become more widely available. It is important for clinicians to determine these titers to permit early vascular complication and treatment.

Behçet disease is a multisystemic inflammatory disorder of unknown etiology that is sometimes associated with thrombosis and vasculitis. Some studies have suggested that BD should be accepted as a hypercoagulable or prothrombotic state.4 Recently, factor V Leiden mutation, prothrombin gene mutation, and homocysteine have been described in the pathogenesis of thrombosis in BD.20,21 In general, aPL Abs are regarded as activating endothelial cells, thus creating a hypercoagulable state.22 We have previously suggested an association between microvascular occlusions and cutaneous vessel vasculitis in the presence of a high level of aPS/PT Abs.14,23 Phosphatidylserine is a regular constituent of the inner leaflet of the cell membrane, which is only exposed on the outside of the cell membrane during apoptosis or by damaged endothelial cells.24 Some studies have shown that prothrombin binds specifically to the surface of apoptotic cells.25,26 We believe that prothrombin binds to apoptotic endothelial cells and combines phosphatidylserine in the SVT. The complexes may cause IgM aPS/PT Ab production in SVT, which would probably be locally produced. These conditions, comprising SVT and elevated aPS/PT Ab level, may be closely related to the pathogenic factors that trigger the development of vasculitis and thrombosis. This study reflects pilot data on a limited number of patients. More experimental work in combination with clinical, histopathological and serological observations is required to further elucidate the role of aPL Abs in BD.

ARTICLE INFORMATION

Correspondence: Tamihiro Kawakami, MD, PhD, Department of Dermatology, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan (tami@marianna-u.ac.jp).

Accepted for Publication: April 10, 2008.

Author Contributions: Dr Kawakami had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study concept and design: Kawakami, Mizoguchi, and Soma. Acquisition of data: Kawakami and Yamazaki. Analysis and interpretation of data: Kawakami and Yamazaki. Drafting of the manuscript: Kawakami and Mizoguchi. Critical revision of the manuscript for important intellectual content: Kawakami and Yamazaki. Statistical analysis: Kawakami and Yamazaki. Administrative, technical, and material support: Kawakami and Soma. Study supervision: Kawakami, Mizoguchi, and Soma.

Financial Disclosure: None reported.

Funding/Support: This work was supported by grants from the Scientific Research Fund of the Ministry of Education, Science, Sports, and Culture, Tokyo, Japan (Grants-in Aid for Scientific Research 16591121 and 18591261).

REFERENCES

Kim  JUChang  HKLee  SS  et al.  Endothelial nitric oxide synthase gene polymorphisms in Behçet's disease and rheumatic diseases with vasculitis. Ann Rheum Dis 2003;62 (11) 1083- 1087
PubMed Link to Article
Önder  MGürer  MA Behçet's disease: an enigmatic vasculitis. Clin Dermatol 1999;17 (5) 571- 576
PubMed Link to Article
Chen  KRKawahara  YMiyakawa  SNishikawa  T Cutaneous vasculitis in Behçet's disease: a clinical and histopathologic study of 20 patients. J Am Acad Dermatol 1997;36 (5, pt 1) 689- 689
PubMed Link to Article
Sakane  TTakeno  MSuzuki  NInaba  G Behçet's disease. N Engl J Med 1999;341 (17) 1284- 1291
PubMed Link to Article
Koç  YGüllü  IAkpek  G  et al.  Vascular involvement in Behçet's disease. J Rheumatol 1992;19 (3) 402- 410
PubMed
Triplett  DA Lupus anticoagulants/antiphospholipid-protein antibodies: the great imposters. Lupus 1996;5 (5) 431- 435
PubMed
Nojima  JIwatani  YSuehisa  EKuratsune  HKanakura  Y The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus. Haematologica 2006;91 (5) 699- 702
PubMed
Atsumi  TIeko  MBertolaccini  ML  et al.  Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum 2000;43 (9) 1982- 1993
PubMed Link to Article
Amengual  OAtsumi  TKoike  T Specificities, properties, and clinical significance of antiprothrombin antibodies. Arthritis Rheum 2003;48 (4) 886- 895
PubMed Link to Article
Shaker  OAy El-Deen  MAEl Hadidi  HGrace  BDEl Sherif  HAbdel Halim  A The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet's disease. Br J Dermatol 2007;156 (1) 32- 37
PubMed Link to Article
Kang  HJLee  YWHan  SHCho  HCLee  KM Anticardiolipin and anti-β2-glycoprotein I antibodies in Behçet's disease. J Korean Med Sci 1998;13 (4) 400- 404
PubMed
Liao  YHHsiao  GHHsiao  CH Behçet's disease with cutaneous changes resembling polyarteritis nodosa. Br J Dermatol 1999;140 (2) 368- 369
PubMed Link to Article
Heller  M Behçet disease (incomplete) and cutaneous polyarteritis nosa. Dermatol Online J 2005;11 (4) 25
PubMed
Kawakami  TYamazaki  MMizoguchi  MSoma  Y High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum 2007;57 (8) 1507- 1513
PubMed Link to Article
International Study Group for Behçet's Disease, Criteria for diagnosis of Behçet's disease. Lancet 1990;335 (8697) 1078- 1080
PubMed
Brandt  JTTriplett  DAAlving  BScharrer  ISubcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH, Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995;74 (4) 1185- 1190
PubMed
Zouboulis  CCBüttner  PTebbe  BOrfanos  CE Anticardiolipin antibodies in Adamantiades-Behçet's disease. Br J Dermatol 1993;128 (3) 281- 284
PubMed Link to Article
Mader  RZiv  MAdawi  MMader  RLavi  I Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behçet's disease. J Rheumatol 1999;26 (11) 2404- 2408
PubMed
Yazici  HChamberlain  MATüzün  YYurdakul  SMüftüoglu  A A comparative study of the pathergy reaction among Turkish and British patients with Behçet's disease. Ann Rheum Dis 1984;43 (1) 74- 75
PubMed Link to Article
Silingardi  MSalvarani  CBoiardi  L  et al.  Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis. Arthritis Rheum 2004;51 (2) 177- 183
PubMed Link to Article
Sarican  TAyabakan  HTurkmen  SKalaslioglu  VBaran  FYenice  N Homocysteine: an activity marker in Behçet's disease? J Dermatol Sci 2007;45 (2) 121- 126
PubMed Link to Article
Pierangeli  SSHarris  EN Probing antiphospholipid-mediated thrombosis: the interplay between anticardiolipin antibodies and endothelial cells. Lupus 2003;12 (7) 539- 545
PubMed Link to Article
Kawakami  TYamazaki  MMizoguchi  MSoma  Y High titer of serum antiphospholipid antibody levels in adult Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis. Arthritis Rheum 2008;59 (4) 561- 567
PubMed Link to Article
Austin  ACampbell  ELane  PElias  E Nodular regenerative hyperplasia of the liver and coeliac disease: potential role of IgA anticardiolipin antibody. Gut 2004;53 (7) 1032- 1034
PubMed Link to Article
D'Agnillo  PLevine  JSSubang  RRauch  J Prothrombin binds to the surface of apoptotic, but not viable, cells and serves as a target of lupus anticoagulant autoantibodies. J Immunol 2003;170 (6) 3408- 3422
PubMed Link to Article
Price  BERauch  JShia  MA  et al.  Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a β2-glycoprotein I-dependent manner. J Immunol 1996;157 (5) 2201- 2208
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Findings from physical examination and histopathological analysis for patient 1. A, Lower extremities showing erythema nodosum–like lesions. B, A lesional skin biopsy specimen of the erythematous macules on the right leg shows typical superficial vein thrombophlebitis in the subcutaneous fat (hematoxylin-eosin, original magnification ×20).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Findings from physical examination and histopathological analysis for patient 2. A, Erythematous eruption with painful erythematous macules over the right extremities. B, A lesional skin specimen from the leg shows superficial vein thrombophlebitis in the middle to deep dermis (hematoxylin-eosin, original magnification ×40). C, Elastic–van Gieson staining reveals local irregular elastic fibers in the blood vessel wall (original magnification ×100).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Findings from physical examination and histopathological analysis for patient 3. A, Erythematous macules and livedo reticularis on right knee. B, Microscopic examination of a specimen from her right lower extremity reveals superficial vein thrombophlebitis with moderate neutrophils and mononuclear cell infiltrations in the dermis and in the septa and lobules of the subcutaneous fat (hematoxylin-eosin, original magnification ×20). C, Elastic–van Gieson staining reveals degenerated elastic fibers in the blood vessel wall (original magnification ×100).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Lupus Anticoagulant (LAC) and Antiphospholipid Antibodies in 3 Patients With Behçet Disease Involving Superficial Vein Thrombophlebitis

References

Kim  JUChang  HKLee  SS  et al.  Endothelial nitric oxide synthase gene polymorphisms in Behçet's disease and rheumatic diseases with vasculitis. Ann Rheum Dis 2003;62 (11) 1083- 1087
PubMed Link to Article
Önder  MGürer  MA Behçet's disease: an enigmatic vasculitis. Clin Dermatol 1999;17 (5) 571- 576
PubMed Link to Article
Chen  KRKawahara  YMiyakawa  SNishikawa  T Cutaneous vasculitis in Behçet's disease: a clinical and histopathologic study of 20 patients. J Am Acad Dermatol 1997;36 (5, pt 1) 689- 689
PubMed Link to Article
Sakane  TTakeno  MSuzuki  NInaba  G Behçet's disease. N Engl J Med 1999;341 (17) 1284- 1291
PubMed Link to Article
Koç  YGüllü  IAkpek  G  et al.  Vascular involvement in Behçet's disease. J Rheumatol 1992;19 (3) 402- 410
PubMed
Triplett  DA Lupus anticoagulants/antiphospholipid-protein antibodies: the great imposters. Lupus 1996;5 (5) 431- 435
PubMed
Nojima  JIwatani  YSuehisa  EKuratsune  HKanakura  Y The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus. Haematologica 2006;91 (5) 699- 702
PubMed
Atsumi  TIeko  MBertolaccini  ML  et al.  Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum 2000;43 (9) 1982- 1993
PubMed Link to Article
Amengual  OAtsumi  TKoike  T Specificities, properties, and clinical significance of antiprothrombin antibodies. Arthritis Rheum 2003;48 (4) 886- 895
PubMed Link to Article
Shaker  OAy El-Deen  MAEl Hadidi  HGrace  BDEl Sherif  HAbdel Halim  A The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet's disease. Br J Dermatol 2007;156 (1) 32- 37
PubMed Link to Article
Kang  HJLee  YWHan  SHCho  HCLee  KM Anticardiolipin and anti-β2-glycoprotein I antibodies in Behçet's disease. J Korean Med Sci 1998;13 (4) 400- 404
PubMed
Liao  YHHsiao  GHHsiao  CH Behçet's disease with cutaneous changes resembling polyarteritis nodosa. Br J Dermatol 1999;140 (2) 368- 369
PubMed Link to Article
Heller  M Behçet disease (incomplete) and cutaneous polyarteritis nosa. Dermatol Online J 2005;11 (4) 25
PubMed
Kawakami  TYamazaki  MMizoguchi  MSoma  Y High titer of anti-phosphatidylserine-prothrombin complex antibodies in patients with cutaneous polyarteritis nodosa. Arthritis Rheum 2007;57 (8) 1507- 1513
PubMed Link to Article
International Study Group for Behçet's Disease, Criteria for diagnosis of Behçet's disease. Lancet 1990;335 (8697) 1078- 1080
PubMed
Brandt  JTTriplett  DAAlving  BScharrer  ISubcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH, Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995;74 (4) 1185- 1190
PubMed
Zouboulis  CCBüttner  PTebbe  BOrfanos  CE Anticardiolipin antibodies in Adamantiades-Behçet's disease. Br J Dermatol 1993;128 (3) 281- 284
PubMed Link to Article
Mader  RZiv  MAdawi  MMader  RLavi  I Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behçet's disease. J Rheumatol 1999;26 (11) 2404- 2408
PubMed
Yazici  HChamberlain  MATüzün  YYurdakul  SMüftüoglu  A A comparative study of the pathergy reaction among Turkish and British patients with Behçet's disease. Ann Rheum Dis 1984;43 (1) 74- 75
PubMed Link to Article
Silingardi  MSalvarani  CBoiardi  L  et al.  Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis. Arthritis Rheum 2004;51 (2) 177- 183
PubMed Link to Article
Sarican  TAyabakan  HTurkmen  SKalaslioglu  VBaran  FYenice  N Homocysteine: an activity marker in Behçet's disease? J Dermatol Sci 2007;45 (2) 121- 126
PubMed Link to Article
Pierangeli  SSHarris  EN Probing antiphospholipid-mediated thrombosis: the interplay between anticardiolipin antibodies and endothelial cells. Lupus 2003;12 (7) 539- 545
PubMed Link to Article
Kawakami  TYamazaki  MMizoguchi  MSoma  Y High titer of serum antiphospholipid antibody levels in adult Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis. Arthritis Rheum 2008;59 (4) 561- 567
PubMed Link to Article
Austin  ACampbell  ELane  PElias  E Nodular regenerative hyperplasia of the liver and coeliac disease: potential role of IgA anticardiolipin antibody. Gut 2004;53 (7) 1032- 1034
PubMed Link to Article
D'Agnillo  PLevine  JSSubang  RRauch  J Prothrombin binds to the surface of apoptotic, but not viable, cells and serves as a target of lupus anticoagulant autoantibodies. J Immunol 2003;170 (6) 3408- 3422
PubMed Link to Article
Price  BERauch  JShia  MA  et al.  Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a β2-glycoprotein I-dependent manner. J Immunol 1996;157 (5) 2201- 2208
PubMed

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For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

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