Correspondence
Behçet's Disease
N Engl J Med 2000; 342:587-589February 24, 2000
- Article
To the Editor:
In their review article, Sakane et al. (Oct. 21 issue)1 asserted that the more severe clinical features of Behçet's disease, such as ocular and central nervous system involvement, are commonly associated with the presence of the HLA-B51 allele. It is generally accepted that the HLA-B51 allele is more common in patients with Behçet's disease than in the general population. However, HLA-B51 positivity generally does not determine the prognosis and response to therapy. A comparative study from Turkey and the United Kingdom found no association between the presence of the HLA-B51 allele and clinical severity of disease.2 The course of Behçet's disease remains unpredictable at the time of diagnosis, and there is no single test to show in whom the disease will run a severe course. Other than the presence of the HLA-B51 allele, several other laboratory findings, such as anticardiolipin-antibody positivity, increased lipoprotein(a) levels, and elevated erythrocyte aggregation, were suggested as predictors of a severe clinical course in patients with Behçet's disease3; however, none have been proved with certainty. A recent study by Demiroglu et al. of 224 patients focused on demographic features and prognosis.4 Male sex and a younger age at onset were associated with the more severe forms of the disease, with vascular thrombotic, ocular, or central nervous system manifestations.
4 ReferencesMeltem Agca, M.D.
Sureyyapasa Sanatorium, Istanbul, Turkey1
Sakane T ,Takeno M ,Suzuki N ,Inaba G . Behçet's disease. N Engl J Med 1999;341:1284-1291
Full Text | Web of Science | Medline2
Yazici H ,Chamberlain MA ,Schreuder I ,D'Amaro J ,Muftuoglu M . HLA antigens in Behçet's disease: a reappraisal by a comparative study of Turkish and British patients. Ann Rheum Dis 1980;39:344-348
CrossRef | Web of Science | Medline3
Demiroglu H ,Yalcin S ,Buyukasik Y ,Ozcebe OI ,Dundar S . Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behçet's disease: a prospective study. Ann Rheum Dis 1998;57:694-696
CrossRef | Web of Science | Medline4
Demiroglu H ,Barista I ,Dundar S . Risk factor assessment and prognosis of eye involvement in Behçet's disease in Turkey. Ophthalmology 1997;104:701-705
Web of Science | Medline
To the Editor:
The detailed review by Sakane et al. fails to mention renal involvement in Behçet's disease. This disease may lead to proliferative glomerulonephritis,1 the nephrotic syndrome due to secondary amyloidosis,2 and renal-vein thrombosis.3 Thus, both acute and chronic renal failure may occur. Whereas glomerulonephritis can occur early in the disease, the nephrotic syndrome tends to be a late complication after years of inflammation. It is helpful to recognize the possibility of renal involvement in this disease to facilitate early institution of renal-replacement therapy.
3 ReferencesChike M. Nzerue, M.D.
Morehouse School of Medicine, Atlanta, GA 303101
Bemelman FJ ,Krediet RT ,Schipper ME ,Arisz L . Renal involvement in Behcet's syndrome: report of a case and a review of the literature. Neth J Med 1989;34:148-153
Web of Science | Medline2
Peces R ,Riesgo I ,Ortego F ,Velasco J ,Alvarez Grande J . Amyloidosis in Behcet's disease. Nephron 1984;36:114-117
CrossRef | Medline3
Werlen D ,Guelpa G ,Robert D . Maladie de Behçet et amyloïdose rénale. Schweiz Rundsch Med Prax 1995;84:533-536
To the Editor:
The succinct description of Behçet's disease by my colleagues in the International Study Group for Behçet's Disease summarizes the current diagnostic and therapeutic aspects of the disorder, sometimes called “Silk Route disease.” However, it fails to make clear that the criteria for diagnosis apply best to patients included in clinical series and do not necessarily apply to all the patients with this disease. Moreover, although involvement of the eye is a leading cause of acquired blindness in Japan,1 this dire consequence occurs less commonly in patients from other geographic areas. Finally, the genetic predisposition to Behçet's disease holds true for patients living in the countries that make up the Silk Route — Turkey, Iran, Iraq, Korea, and Japan — but may not apply to the few patients in the West. For the latter patients, the term “Behçet's syndrome” seems more appropriate, since the symptoms, signs, severity, and course, as well as underlying diseases, differ from those of true Behçet's disease.2
2 ReferencesGeorge E. Ehrlich, M.D.
University of Pennsylvania, Philadelphia, PA 191041
Shimizu T ,Ehrlich GE ,Inaba G ,Hayashi K . Behçet's disease (Behçet syndrome). Semin Arthritis Rheum 1979;8:223-260
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Ehrlich GE . Behcet disease and the emergence of thalidomide. Ann Intern Med 1998;128:494-495
Web of Science | Medline
To the Editor:
Sakane et al. indicate that serum IgD can be used as a diagnostic marker because levels may be elevated in patients with active disease. We seriously doubt the usefulness of this test.
We studied serum samples from 30 patients with Behçet's disease and measured IgD using a sensitive enzyme-linked immunosorbent assay.1 Only one patient had an elevated serum IgD value (240 U per milliliter; normal value, <100 U per milliliter). In another study, no patient had elevated IgD levels.2 On the basis of these findings, we suggest that normal IgD levels could be used to distinguish Behçet's disease from the hyper-IgD syndrome, because the latter sometimes mimics Behçet's disease.
2 ReferencesJoost P.H. Drenth, M.D., Ph.D.
University Hospital St. Radboud, 6500 HB Nijmegen, the NetherlandsAvi Livneh, M.D.
Sheba Medical Center, Tel-Hashomer, Israel1
Brezniak N ,Shtrasburg S ,Langevitz P , et al. Serum IgD as a discriminator between the two periodic febrile syndromes hyperimmunoglobulinaemia D syndrome and Behçet's disease. Ann Rheum Dis 1998;57:255-256
CrossRef | Web of Science | Medline2
Scully C ,Boyle P ,Yap PL . Immunoglobulins G, M, A, D and E in Behçet's syndrome. Clin Chim Acta 1982;120:237-242
CrossRef | Web of Science | Medline
To the Editor:
Streptococcus sanguis and other microorganisms are either directly or indirectly causative in the pathogenesis of Behçet's disease, because they trigger immunopathologic responses. Sakane et al. mentioned streptococci, but they did not mention that penicillin G benzathine can be used for prophylaxis against inflammatory attacks and for treatment of the disease. We and our colleagues1-3 found that a single injection of 1.2 million units of penicillin G benzathine every three weeks resulted in a reduction in episodes and prolonged the duration of episode-free intervals, especially in patients with Behçet's disease who had mucocutaneous disease and arthritis. This benefit may be due to the eradication of recurrent focal streptococcal infections that trigger the inflammatory episodes of Behçet's disease.
3 ReferencesIbrahim C. Haznedaroglu, M.D.
Osman I. Özcebe, M.D.
Semra V. Dündar, M.D.
Hacettepe University Medical School, TR-06100 Ankara, Turkey1
Haznedaroglu IC, Demiroglu H, Özcebe OI, Özdemir O, Dündar S. Benzathine-penicillin in the prophylaxis and treatment of Behçet's disease. In: Boki KA, Drosos AA, Moutsopoulos HM, Tzioufas AG, Vlachoyiannopoulos PG, eds. Proceedings of the 7th Mediterranean Congress of Rheumatology, Athens, Greece, June 16–18, 1994. Bologna, Italy: Monduzzi Editore, 1995:185-8.
2
Calguneri M ,Kiraz S ,Ertenli I ,Benekli M ,Karaarslan Y ,Celik I . The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behçet's disease. Arthritis Rheum 1996;39:2062-2065
CrossRef | Web of Science | Medline3
Calguneri M ,Ertenli I ,Kiraz S ,Erman M ,Celik I . Effect of prophylactic benzathine penicillin on mucocutaneous symptoms of Behçet's disease. Dermatology 1996;192:125-128
CrossRef | Web of Science | Medline
To the Editor:
. . . The first description of patients with Behçet's disease appears to be by Hippocrates, in the fifth century b.c., in his third book of epidemiology:
There were other forms of fever. . . . Many developed aphthae, ulcerations. Many ulcerations about the genital parts. . . . Watery ophthalmies of a chronic character, with pains; fungus excretions of the eyelids externally, internally, which destroyed the sight of many persons. . . . There were fungous growths on ulcers, and on those localised on the genital organs. Many anthraxes through the summer. . . . other great affections; many large herpetes.1
1 ReferencesTsung O. Cheng, M.D.
George Washington University, Washington, DC 200371
Kaklamani VG ,Vaiopoulos G ,Kaklamanis PG . Behçet's disease. Semin Arthritis Rheum 1998;27:197-217
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We appreciate the responses to our review article. We focused on the most typical features of the disease, and not on every known clinical manifestation or on the regional differences in this disease.
There are differences in the clinical features between patients who live in the countries that make up the Silk Route and those who do not, as pointed out by Dr. Ehrlich. These differences may arise from different genetic backgrounds, differences in environmental factors, including infectious microorganisms, or both. Despite these differences, the autoimmune responses to the heat-shock protein have been shown to be an important etiopathogenic factor in patients from England, Turkey, and Japan.1-3 The fact that patients from these countries react to the same etiologic factor strongly suggests the existence of a single disease entity.
As pointed out by Dr. Nzerue, renal lesions, including glomerulonephritis, IgA nephropathy, renal-vein thrombosis, and amyloidosis, may develop in patients with Behçet's disease.4 Esophageal lesions and hematopoietic disorders may also develop. Gastrointestinal involvement is more frequent in far eastern Asia than in any other part of the world, whereas renal disease rarely occurs in Japan.
We agree with Dr. Agca that male sex and a younger age at onset are independent risk factors for severe forms of the disease with ocular and central nervous system manifestations. It is hard to predict the prognosis of patients with Behçet's disease on the basis of laboratory tests. Although some HLA-B51–positive patients may have a relatively good prognosis, HLA-B51 remains a prognostic factor in this disease with respect to both morbidity and mortality.5 We do not agree about the association of the presence of anticardiolipin antibodies and increased lipoprotein(a) levels with severe forms of the disease. Rather, the presence of anticardiolipin antibodies suggests a diagnosis of antiphospholipid syndrome, not of Behçet's disease.
Although elevated serum IgD is observed in patients with IgD myeloma and the hyper-IgD syndrome, the diseases are extremely rare. In contrast, an elevated serum IgD level is detected in more than 10 percent of patients with Behçet's disease during an ocular attack or active disease. We agree that microbial infections are implicated in Behçet's disease, but the prophylactic use of antibiotics is not part of standard therapy. Indeed, we have experience with an unsuccessful trial of antibiotics for prophylaxis against Behçet's disease. Once triggered by bacterial or cross-reactive antigens, autoimmune responses, but not microbial infection, are an important part of the pathogenesis of this disease.
5 ReferencesTsuyoshi Sakane, M.D., Ph.D.
Mitsuhiro Takeno, M.D., Ph.D.
Noboru Suzuki, M.D., Ph.D.
St. Marianna University School of Medicine, Kanagawa 216-8511, Japan1
Pervin K ,Childerstone A ,Shinnick T , et al. T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behçet's disease. J Immunol 1993;151:2273-2282
Web of Science | Medline2
Tasci B ,Direskeneli H ,Serdaroglu P ,Akman-Demir G ,Eraksoy M ,Saruhan-Direskeneli G . Humoral immune response to mycobacterial heat shock protein (hsp)65 in the cerebrospinal fluid of neuro-Behçet patients. Clin Exp Immunol 1998;113:100-104
CrossRef | Web of Science | Medline3
Kaneko S ,Suzuki N ,Yamashita N , et al. Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behçet's disease (BD) in Japan. Clin Exp Immunol 1997;108:204-212
CrossRef | Web of Science | Medline4
Kaklamani VG ,Vaiopoulos G ,Kaklamanis PG . Behçet's disease. Semin Arthritis Rheum 1998;27:197-217
CrossRef | Web of Science | Medline5
Ohno S ,Ohguchi M ,Hirose S ,Matsuda H ,Wakisaka A ,Aizawa M . Close association of HLA-Bw51 with Behçet's disease. Arch Ophthalmol 1982;100:1455-1458
Web of Science | Medline
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