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Familial atrioventricular block: Predisposition not associated with the hla system
LETTERS
TO THE EDITOR
matologic manifestations. Certainly, at least two of the aforementioned should be present to attach a label of even “incomplete Reiter’s syndrome.” The case report of Cooper and Ferriss indicated only arthritis. Reiter’s syndrome may be one of the types of reactive arthritis, but all reactive arthritis is not Reiter’s syndrome. DAVISON, M.D., F.A.C.P. Manhattan Medical Group, P.C. East 6 1st Street Center 425 East 61st Street New York, New York 10021
SELVAN
Submitted
October
6, 1986, and accepted
October
29, 1986
The Reply: We appreciate Dr. Davison’s comments and agree with him that the terms reactive arthritis and Reiter’s syndrome should not be used interchangeably. With the recognition of the association of HLA-627 and Reiter’s syndrome, the term “incomplete Reiter’s syndrome” was used for patients who presented with only arthritis [I]. In a recent review, Keat [2] emphasized the markea similarities between Reiter’s syndrome and reactive arthritis, but suggested that the term Reiter’s syndrome be reserved for patients who present with additional features of the classic triad. We agree with this classification, and in our report, the patient’s condition was called reactive arthritis. M. COOPER, M.D. JOHN A. FERRISS, M.D. Rheumatology and Clinical Immunology Division University of Vermont College of Medicine Burlington, Vermont 05405 SHELDON
1. 2.
Arnett FC, McCluskey OE, Schacter BZ, Lordon RE: Incomplete Reiter’s syndrome. Ann Intern Med 1976; 84: 8-12. Keat A: Reiter’s syndrome and reactive arthritis in perspective. N Engl J Med 1983; 309: 1606-1615.
FAMILIAL POSITION SYSTEM
ATRIOVENTRICULAR NOT ASSOCIATED
February
1987
M.D., Ph.D. of Medicine ERNA WLLER, M.D., Ph.D. Department of Clinical Immunology Karolinska Institute Huddinge Hospital S-141 66 Huddinge, Sweden LENNART
BERGFELDT,
Cardiac Division,
Department
BLOCK: PREDISWITH THE HLA
To the Editor: Many cardiac disorders show familial aggregation, and large kindreds with atrioventricular conduction abnormalities have been described [ 11. The genetic background is unknown and different modes of inheritance have been suggested. We have recently reported a connection between, on the one hand, the immunogenetic marker HLA827 and associated rheumatic disorders, and on the other hand, a substantial proportion of the group of Caucasian males-but not females-who require pacemaker treatment because of symptomatic bradycardias [2-41. Familial aggregation of ankylosing spondylitis and the other HLAB27associated rheumatic disorders has long been recognized. Consequently, the question arose whether familial aggregation of conduction abnormalities of the heart has anything to do with HLA-B27 or other HLA alleles.
386
Among approximately 400 patients with permanent pacemakers, three pairs of siblings were identified. All six patients had complete heart block diagnosed at ages between 5 1 and 69 years. Two pairs were brother-sister, one of whom had a cousin, who was pacemaker-treated, but died before HLA typing could be performed. The last pair was brother-brother, one of whom had ankylosing spondylitis, HLA-B27, and at age 51, complete heart block with narrow QRS complexes, indicating a proximal block consistent with previous reports [5,6]. His brother, who was B27-negative, had muscular atrophy of spinal origin. He had also had two myocardial infarctions six years prior to the need for pacing, which occurred at age 66. These brothers shared the haplotype A3B7. However, two different pathophysiologic mechanisms seem possible in this pair of brothers, HLA-B27-associated inflammation and coronary heart disease, respectively. The siblings of the other two pairs did not share haplotypes within the class I molecules of the HLA system. One pair had A1,2, B6,14, C- and A2, 11, B5,15, C-, and the other A3,10, B7(41,53?), C- and A2,9, B7,15, Cw3,4. It therefore seems unlikely that the familial predisposition to complete heart block in our families was associated with the HLA system. As several different disease mechanisms may lead to the development of atrioventricular conduction disturbances, not necessarily the same mechanism may be the cause in different kindreds. Hence, our observations do not excluded HLAassociated heart block in other families. In accordance with previous observations on familial heart block, the predisposition was not sex-linked in our group of patients. Notably, all six patients had blood group 0, which otherwise is found in around 40 percent of the Swedish population. This could be a coincidence, or may indicate a connection with the blood group system or other genes located on the ninth pair of chromosomes.
The American
Journal
of Medicine
Volume
1.
2. 3.
4.
5.
6.
Lynch HT, Mohiuddin S, Moran J, et al: Hereditary progressive atrioventricular conduction defect. Am J Cardiol 1975; 36: 297-301. Bergfeldt L: HLA-B27-associated rheumatic diseases with severe cardiac bradyarrhythmias. Am J Med 1983; 75: 210-215. Bergfeldt L, Moller E: Complete heart block-another HLA-B27associated disease manifestation. Tissue Antigens 1963; 21: 385-390. Bergfeldt L, Moller E: Pacemaker treated women with heart block have no increase in the frequency of HLA-B27 and associated rheumatic disorders in contrast to men-a sex-linked difference in disease susceptibility. J Rheumatol (in press). Nitter-Hauge S, Otterstad JE: Characteristics of atrioventricular conduction disturbances in ankylosing spondylitis (Mb. Bechterew). Acta Med Stand 1981; 210: 197-200. Bergfeldt L, Vallin H, Edhag 0: Complete heart block in HLA-B27associated disease. Br Heart J 1984; 51: 184-188. Submitted
82
October
27, 1986,
and accepted
October
30, 1986
TO THE EDITOR
matologic manifestations. Certainly, at least two of the aforementioned should be present to attach a label of even “incomplete Reiter’s syndrome.” The case report of Cooper and Ferriss indicated only arthritis. Reiter’s syndrome may be one of the types of reactive arthritis, but all reactive arthritis is not Reiter’s syndrome. DAVISON, M.D., F.A.C.P. Manhattan Medical Group, P.C. East 6 1st Street Center 425 East 61st Street New York, New York 10021
SELVAN
Submitted
October
6, 1986, and accepted
October
29, 1986
The Reply: We appreciate Dr. Davison’s comments and agree with him that the terms reactive arthritis and Reiter’s syndrome should not be used interchangeably. With the recognition of the association of HLA-627 and Reiter’s syndrome, the term “incomplete Reiter’s syndrome” was used for patients who presented with only arthritis [I]. In a recent review, Keat [2] emphasized the markea similarities between Reiter’s syndrome and reactive arthritis, but suggested that the term Reiter’s syndrome be reserved for patients who present with additional features of the classic triad. We agree with this classification, and in our report, the patient’s condition was called reactive arthritis. M. COOPER, M.D. JOHN A. FERRISS, M.D. Rheumatology and Clinical Immunology Division University of Vermont College of Medicine Burlington, Vermont 05405 SHELDON
1. 2.
Arnett FC, McCluskey OE, Schacter BZ, Lordon RE: Incomplete Reiter’s syndrome. Ann Intern Med 1976; 84: 8-12. Keat A: Reiter’s syndrome and reactive arthritis in perspective. N Engl J Med 1983; 309: 1606-1615.
FAMILIAL POSITION SYSTEM
ATRIOVENTRICULAR NOT ASSOCIATED
February
1987
M.D., Ph.D. of Medicine ERNA WLLER, M.D., Ph.D. Department of Clinical Immunology Karolinska Institute Huddinge Hospital S-141 66 Huddinge, Sweden LENNART
BERGFELDT,
Cardiac Division,
Department
BLOCK: PREDISWITH THE HLA
To the Editor: Many cardiac disorders show familial aggregation, and large kindreds with atrioventricular conduction abnormalities have been described [ 11. The genetic background is unknown and different modes of inheritance have been suggested. We have recently reported a connection between, on the one hand, the immunogenetic marker HLA827 and associated rheumatic disorders, and on the other hand, a substantial proportion of the group of Caucasian males-but not females-who require pacemaker treatment because of symptomatic bradycardias [2-41. Familial aggregation of ankylosing spondylitis and the other HLAB27associated rheumatic disorders has long been recognized. Consequently, the question arose whether familial aggregation of conduction abnormalities of the heart has anything to do with HLA-B27 or other HLA alleles.
386
Among approximately 400 patients with permanent pacemakers, three pairs of siblings were identified. All six patients had complete heart block diagnosed at ages between 5 1 and 69 years. Two pairs were brother-sister, one of whom had a cousin, who was pacemaker-treated, but died before HLA typing could be performed. The last pair was brother-brother, one of whom had ankylosing spondylitis, HLA-B27, and at age 51, complete heart block with narrow QRS complexes, indicating a proximal block consistent with previous reports [5,6]. His brother, who was B27-negative, had muscular atrophy of spinal origin. He had also had two myocardial infarctions six years prior to the need for pacing, which occurred at age 66. These brothers shared the haplotype A3B7. However, two different pathophysiologic mechanisms seem possible in this pair of brothers, HLA-B27-associated inflammation and coronary heart disease, respectively. The siblings of the other two pairs did not share haplotypes within the class I molecules of the HLA system. One pair had A1,2, B6,14, C- and A2, 11, B5,15, C-, and the other A3,10, B7(41,53?), C- and A2,9, B7,15, Cw3,4. It therefore seems unlikely that the familial predisposition to complete heart block in our families was associated with the HLA system. As several different disease mechanisms may lead to the development of atrioventricular conduction disturbances, not necessarily the same mechanism may be the cause in different kindreds. Hence, our observations do not excluded HLAassociated heart block in other families. In accordance with previous observations on familial heart block, the predisposition was not sex-linked in our group of patients. Notably, all six patients had blood group 0, which otherwise is found in around 40 percent of the Swedish population. This could be a coincidence, or may indicate a connection with the blood group system or other genes located on the ninth pair of chromosomes.
The American
Journal
of Medicine
Volume
1.
2. 3.
4.
5.
6.
Lynch HT, Mohiuddin S, Moran J, et al: Hereditary progressive atrioventricular conduction defect. Am J Cardiol 1975; 36: 297-301. Bergfeldt L: HLA-B27-associated rheumatic diseases with severe cardiac bradyarrhythmias. Am J Med 1983; 75: 210-215. Bergfeldt L, Moller E: Complete heart block-another HLA-B27associated disease manifestation. Tissue Antigens 1963; 21: 385-390. Bergfeldt L, Moller E: Pacemaker treated women with heart block have no increase in the frequency of HLA-B27 and associated rheumatic disorders in contrast to men-a sex-linked difference in disease susceptibility. J Rheumatol (in press). Nitter-Hauge S, Otterstad JE: Characteristics of atrioventricular conduction disturbances in ankylosing spondylitis (Mb. Bechterew). Acta Med Stand 1981; 210: 197-200. Bergfeldt L, Vallin H, Edhag 0: Complete heart block in HLA-B27associated disease. Br Heart J 1984; 51: 184-188. Submitted
82
October
27, 1986,
and accepted
October
30, 1986