656 Ti, CANADIN MEDICAL ASsOcIATIoN JOURNAL [Nov. 1930

SYPHILIS OF THE AND HEART* A CLINICAL STUDY BY SAMUEL S. RIVEN, M.D., Ann Arbor, Mich., and J. FEIGENBAUM, M.D., Montreal THIS article presents a summary of the clinical can be demonstrated microscopically in findings in a series of 74 patients with practically 100 per cent of the cases syphilitic observed at Very different is the case in the syphilitic female. the University Hospital, Arn Arbor, between In a large proportion of such, no characteristic July, 1925 and July, 1927. Seven of these gross or microscopic syphilitic lesions can be patients were subjected to autopsy. In the found in either aorta or heart." remaining instances the diagnosis was made on Racial incidence.-Sixty-four of the patients the history, and the clinical and laboratory here reported belonged-to the white race and findings. No doubtful cases were included. 10 to the coloured r4k. The proportion in The clinical diagnoses are summarized in Table I. Scott's series between white and coloured in- There is an extensive literature dealing with dividuals was 34 to 41. Paullin found evidence this subject. Among the more important studies of cardiovascular in 39 per cent of are those of Longcope', Allbutt23, and Reid45. 662 negroes who had syphilis. This percentage We have compared our data with the findings is apparently not any greater than occurs in of these and various other authors. the white population with syphilis. No definite conclusion can be drawn regarding the pre- TABLE I. disposition of negroes to syphilis of the circulatory Clinical Diagnosis No. of Cases apparatus, because the figures from various parts without of the country vary with the proportion of ...... 35 47 Syphilitic without aneurysm negroes in the total population. or aortic insufficiency...... 14 19 Age incidence.-The relationship of cardio- Aneurysm...... 13 18 Aneurysm and aortic insufficiency. 9 11 vascular syphilis to age is given in Table II. Syphilitic myocarditis...... 3 4 TABLE II. 74 100 Ages No. of Cases Per Cent ETIOLOGICAL CONSIDERATIONS Authors' Longcope's Authors' Longcope's Series Series Series Series Relationship of sex to the incidence of cardio- 20-30 0 19 0 30.1 vascular syphilis.-Of the total number of 31-40 7 13 9 20.6 patients, 64 were males and 10 were females, 41-50 33 19 45 30.1 51-60 23 7 31 11.1 an incidence of 6.4 to 1 in favour of males. 61- 1 1 5 -15 8.0 In cases on which autopsy. was performed Reid4 found a ratio of 3 to 1; Scott6 6 to 1, and Clawson 74 63 100 99.9 and Bell7 4.7 to 1; while in clinical cases Reid By far the largest number of our cases fell found a ratio of 11 fo 1 (out patients), and Paullin8 into the fifth and sixth decades, while the majority 4 to 1. One might expect to find a greater of Longcope's cases were found in the third and preponderance of males in autopsied than in fifth decades, with- an equal number in each of clinical cases, for according to Warthin9 "Sy- these age groups. A comparison of the two philitic lesions in the aorta and heart of the male series reveals a rather striking difference in the third, fifth, and sixth decades, with the greatest *From the Department of Internal Medicine, Uni- versity Hospital, University of Michigan, Ann Arbor, discrepancy in the third. As will be noted, Michigan. almost one-third of Longcope's patients were Nov. 1930] RIVEN AND FEIGENBAUM: SYPHILIS OF THE AORTA AND HEART 657

between 20 and 70 years of age, while none of some complaint, or the symptom which urged our patients fell within that age period. Also, him to seek medical advice. Although it was while one-half of Longcope's patients were difficult to be certain of the presenting symptom between 20 and 40 years old we found a much in every instance, it was obtainable in the ma- smaller percentage in this group. In fact, 67 jority of patients. The most frequent was per cent of the patients were between 40 and 55 dyspncea on exertion, in 44 patients, or 59 per years old. The average age of all patients was cent of the total number. Next in order of 50 years, with extremes of 32 and 74 years. frequency was pain in the chest, arms or abdomen, Most authors place the commonest age inci- in 19 patients, or 25 per cent. Palpitation was dence of syphilitic heart disease between 40 the chief complaint in 2 patients; "swelling of and 50 years. Reid gives the average age as the ankles" in 2 instances, and "nervousness" 44 years, with age limits between 21 and 73 years. in 2 others. Of the 3 remaining patients, one Allbutt2 gives the age period of greatest incidence presented as his chief difficulty "painful heels", as 35 to 50. Benary (quoted by Allbutt in the another dizziness, and the third hoarseness. It above reference) gives the average age as 48.6 will be seen that 84 per cent of the patients with years. Brooks11 in a study of 200 cases found syphilitic cardiovascular disease had as their the average age in women to be 38 years, and in presenting symptom either dyspnoea on exertion men 44 years. Scott sets the average age at or pain. The duration of the chief complaint about 40 years, with limits of 29 and 76 years. varied between 2 weeks and 16 years. In about The mean of Coombs'10 cases was only 35 years. three-quarters of the cases, however, the chief In 80 per cent of Paullin's patients, the disease complaint had been present between 2 weeks was seen before the fiftieth year. This author and 2 years before the patient came to the points to the fact that syphilitic aortitis can hospital. occur in adolescence, one of his patients being Dyspncea.-Dyspncea on exertion as a feature 17 years old and another 22 years old. at, some time during the patient's illness, and not necessarily as a presenting symptom, occurred SYMPTOMS in 67 patients or 90 per cent. Longcope found The interval between primary syphilitic dyspnoea to be one of the first symptoms in and onset of symptoms.-This information was about one-half of his cases, and Reid found available in only 39 of the cases. The shortest it in two-thirds of his series. lapse of time between the infection and the Paroxysmal dyspnwa.-Paroxysmal dyspncea development of symptoms was 6 years, the. appeared in 13, or 17 per cent, of our cases, and longest 49 years; the average interval was 24 in 9, or 14 per cent, of Longcope's patients. In years. An interval of 6 to 20 years elapsed Scott's experience, only few cases of syphilitic between the primary infection and clinical aortitis without aortic insufficiency presented disease in one-third of the cases and a period of typical paroxysmal nocturnal dyspncea. Keefer 21 to 30 years in half of the cases. So that in and Resnik"2 also found this symptom to be very five-sixths of the 39 cases, symptoms appeared common in aortitis with aortic insufficiency; of between 6 and 30 years following the infection. their 28 patients 25, or 89 per cent, had From his studies, Longcope concluded that the paroxysmal dyspncea. In another series of 24 average interval between infection and the patients with uncomplicated syphilitic aortitis, occurrence of symptoms was 16 years, the limits collected by Keefer and Resnik, not one being 3 and 35 years. Coombs found this complained of paroxysms of dyspncea. So far lapse of time to be- about 20 years., Scott ob- as the high incidence of paroxysmal dyspncea served the interval between infection and death in cases with aortic insufficiency is concern- in 34 male patients to range from 5 to 44 years, ed our experience has been different from the average being 20 years. It is worthy of note that of the last mentioned authors. Only here that many authors have reported syphilitic 9 of our 42 patients with aortic insufficiency had infection of the heart and aorta during the paroxysmal dyspncea. Moreover, of the total secondary stage. Valda (quoted by Allbutt) number of 13 cases with paroxysms of dyspncea, reported a case of infection of the mediastinal 4 had aortitis without aortic insufficiency. glands while the chancre was still present. Longcope, who was one of the first of American Presenting symptom.--By "presenting symp- authors to call attention to the occurrence of tom?' we mean the patient's chief or most trouble- paroxysmal dyspneea in syphilitic aortitis, '658T6E8 CANN:A.DI MsncAL ASsoCLATION JOURNAL[[Nov. 1930

attributed the attacks of to were unable to find any definite data regarding. reflex stimuli from the root of the aorta. the relative frequency of cardiac enlargement in Allbutt's explanation of this phenomenon is that syphilitic heart disease, as determined by clinical it is due to an irritation of the recurrent laryngeal means. However, reference is made to the nerve with consequent laryngeal spasm.. Keefer weight of the heart in certain pathological studies and Resnik offered no explanation of the on cardiovascular syphilis. Scott and Saphir" paroxysms of dyspncea, but maintained that state that the majority of hearts with syphilitic they occurred generally in patients with very aortic insufficiency weighed about 500 grams, large hearts. Twelve of our 13 patients with and Clawson and Bell give the average size of attacks of dyspncea had huge hearts, while the the heart in syphilitic aortitis as 620 grams for 13th had an aneurysm with a heart of normal men and 400 'grams for women. It seems size. Whatever the mechanism of the production apparent. then, that increase in the size of the of paroxysmal dyspncea may be, we are justified heart as determined by the ordinary examination in concluding that paroxysmal dyspncea in is a fairly constant, though not characteristic, syphilitic cardiovascular disease is usually clinical sign in syphilitic heart disease. associated with marked cardiac enlargement. Diastolic murmur at the base.-The character- Pain.-Pain was a symptom in 37, or in 50 istic murmur of aortic insufficiency at the second per cent, of our patients. In 31 of these it was right costal cartilage or along the left border of located 'over the precordium; in 3 it was sub- the sternum was heard in 42, or 56 per cent, of sternal; in 2 it was epigastric; and in 1 it was the cases. In 35 of the cases with an aortic right thoracic. Longcope found pain as an diastolic murmur enlargement of the heart was important symptom in 29 of his 63 patients, or found both by physical and Roentgen-ray 46 per cent. In Brooks' series of 200 patients, examination. Clawson and Bell, with their pain was complained of by 119, or 59 per cent. autopsy material, have called attention to the While most of our patients described their pain fact that cardiac enlargement is almost always as being in the precordium, Reid has found it associated with aortic insufficiency, and, as generally spoken of as "substernal". Typical already stated, Scott and Saphir made the same angina pectoris occurred in 5 of our cases (6 per observation. Our clinical data support these cent) and in 18 of Brooks' patients (9 per cent). findings. Although pain in syphilitic heart disease is Reference to the presence or absence of a usually attributed to a narrowing of the mouths collapsing pulse was made in 60 of the case of the coronary , this is far from being a records reviewed. Corrigan's "water-hammer" settled question. Allbutt2 has stated quite pulse was observed in 23. The average pulse emphatically that the closure of the coronaries pressure in this series was 97 mm. of is not the cause of the pain in syphilitic aortitis. mercury, which bears out the well known Hordert3 is convinced that pain is by far the clinical fact that a collapsing pulse is frequently most important symptom of syphilitic aortitis. associated with a high pulse pressure. While Practically all the authors whose opinion we have a Corrigan pulse is emphasized in the diagnosis consulted on this subject express the same con- of aortic insufficiency, it is noteworthy that only clusion. Pain is, perhaps, the most characteristic in a little over one-half of these was a Corrigan symptom of syphilitic aortitis, but its importance pulse present. in diagnosis should not be over-emphasized, Modified aortic second sound.-A changed aortic because it may be absent in about half the cases. second sound was found by itself or in association Other symptoms.-Palpitation of the heart was with a diastolic murmur at the base in 40 patients met with in 61 per cent of the cases, and puffiness (54 per cent). Ever since Allbutt called attention or swelling of the ankles in 35 per cent. Neither to the altered character of the aortic second of these symptoms is, of course, significant in the sound, most clinicians have confirmed this diagnosis of syphilitic cardiovascular disease. observation. The second sound has been variously described as "accentuated", "ringing", FINDINGS ON PHYSICAL EXAMINATION " hollow ", or " metallic " in quality. Hoover"5 Enlargement of the heart.-The teleoroent- believed that the diagnosis of early syphilitic genogram, or physical examination, showed aortitis was possible by physical signs alone in definite cardiac enlargement in 61, or 83 per cent, the majority of instances. This author pointed of our patients. In the recent literature we out that many of the early physical signs of NOV. 1930] RIEN AND FEIGENBAUM: SYPHILIS OF THE AORTA AND HEART 659 *.-17-A,LX '1110-

aortitis are the result of a lengthening of the.. TABLE III. Number of Cases Spinal fluid Wassermann reaction positive.... 8 ascending arch with some tortuosity, so that the Spinal fluid Wassermann reaction negative, arch approaches the surface of the chest more with definite signs of central nervous system syphiis...... 4;...... 4 closely than it does normally. He thus explained Spinal fluid Wassermann reaction not obtained, the accentuated second sound and the systolic with definite signs of central nervous system syphilis...... 8 thrust at the right of the sternum. A modified Total number of cases with suspected central aortic second sound does not always indicate nervous system syphilis...... 20 syphilitic aortitis, as and arterio- series is -due to the fact- that in a number of sclerotic changes of the aorta must also be con- suspected cases examination of the spinal fluid sidered. was not made. Murmurs at the apex.-A systolic murmur was audible at the apex in 30 patients. This was LABORATORY STUDIES IN SYPHILITIC usually described as being soft and high pitched. HEART DIsEASE In 17 patients a diastolic murmur was heard at The Roentgenogram.-In 1913 Longcope called the apex; in 14 of these it was soft and blowing, attention to the dilatation of the great vessels in and in 3 it was rumbling in quality. There was syphilitic aortitis. He noted that the dilatation no reason to suspect mitral of rheumatic may take the form on the x-ray film of a cone with origin in the last three patients. Warthin16 its apex pointing towards or away from the has never seen syphilis attack the mitral valve. heart, and also that early cases may show nothing Thus, in a little less than one quarter of the total more than a slightly bulging shadow to the right number, and in more than one-third of the cases of the vertebral column in the region of the with an aortic diastolic murmur, an apical ascending aorta. Longcope further maintained diastolic murmur was present. Thayer is quoted that with the extension of the syphilitic process by Osler and McCrae17 as stating that an apical to the transverse and descending segments of diastolic murmur occurs in half the cases with the aorta, the aortic knob disappears. Hickey"8 uncomplicated aortic insufficiency. has described a new sign frequently seen in The .-In 18, or nearly one- aortic syphilis. There occurs, on the lateral quarter of the patients, the pulse pressure was roentgenogram of the chest, an angulation at more than 100 mm. of mercury; in 25, or one- the junction of the ascending and transverse third of the cases, it was above 90; and in 34 parts of the aorta, which is the result of a patients, or almost one-half, it was over 80 mm. lengthening of this vessel. There is also an In those patients who had a pulse pressure of increased visibility of the aortic arch in the 80 mm., 32 of 34 had the diastolic murmur of lateral projection. One of the most important aortic insufficiency. There apparently are no fluoroscopic signs is expansile pulsation of the characteristic blood pressure changes in syphilitic enlarged aorta, which is the earliest sign of aortitis except when aortic insufficiency is present. aneurysm. There is nothing specially character- This observation conforms with the opinion of istic of the syphilitic heart itself on the Roentgen- most authors on this subject. ray film. SYPHILIS OF THE AORTA AND CENTRAL NERVOUS The Wassermann reaction.-The complement SYSTEM fixation test was positive in 66, or 89 per cent, of The frequent association of syphilis of the our patients; doubtful in 2, or 2 per cent; and negative in 7, or 9 per central nervous system and syphilitic aortitis cent. has been known for a long time, and was first TABLE IV. mentioned by Berger and Rosenback in 1879 Relationship between cardio-vascular syphilis and a positive blood Wassermann test: (quoted by Allbutt). In many cases of syphilitic Author Percentage with positive reactions aortitis, central nervous system symptoms are Reid9 83 Eicke3 81 the only clinical evidence of syphilis. Scott1I 80 There was clear evidence of syphilis of the Citron4 60 central nervous system in only 10 per cent of Authors 91 our patients. Allbutt cites Goldscheider, who If doubtful Wassermann reactions may be found 39 cases of tabes in 136 cases of syphilis considered significant, then as will be seen by of the aorta. The rather low percentage of cases reference to Table IV., 91 per cent of these of central nervous system involvement in our patients had a positive complement fixation test. 660 TEmTHE CA.NTADMM,CANADiAN MmicALAgsocIATIONM.rncAL ASSOCIATION JOURNAL [Nov. 1930

This is in accord with most of the statistical aortic insuiciency. Pain-was absent in one-half studies heretofore recorded. Complement fixa- of the cases. An increase in the size of the heart, tion depends upon the persistence of immune demonstrated by physical and Roentgen-ray bodies in the serum, whereas syphilis of the heart examination, is a fairly constant clinical sign in and aorta may be present after these bodies have syphilitic heart disease. Cardiac enlargement in disappeared. Hence the Wassermann reaction syphilitic heart disease is almost always associated should not be the last resort in diagnosis, and, with aortic insufficiency. A changed aortic as has been pointed out by others, a diagnosis of second sound was found by itself or in association cardiovascular syphilis can safely be made in the with a diastolic murmur at the base in 40 cases. absence of a positive Wassermann reaction if In half the patients the pulse pressure was over the clinical picture suggests the disease. 80 mm. of mercury. There are apparently no The electrocardiogram.-In this series 67 of characteristic blood pressure changes in syphilitic the patients had had electrocardiograms. aortitis except when aortic insufficiency is Eighteen of these were normal, while the re- present. In 10 per cent of the cases there was mainder showed abnormalities of various kinds. syphilis of the central nervous system. The The most common finding observed was left blood. Wassermann reaction was positive in 91 ventricular preponderance, which occurred in per cent of the cases. almost 40 per cent of the patients. The other Our thanks are due to Dr. Frank N. Wilson for his variations were of the type which one might see encouragement and invaluable suggestions in this study. that in any other group of cardiac patients, so REFERENCES no clue the electrocardiogram in itself offered 1. LONGCOPE, Arch. of Int. Med., 2:15, June, 1913. to the diagnosis. The deviations from the 2. ALLBuITT, Diseases of the Arteries including Angina normal which influence prognosis were, of course, Pectoris, 2: 167, Macmillan & Co., London, 1915. as useful with syphilis of the cardiovascular 3. ALLBuTT, Brit. M. J., 1: 177, August 6, 1921. 4. REID, Boston Med. and Surg. J., 183: 67, July 15, 1920. system as with any other type of cardiac disease. 5. REID, Boston Med. and Surg. J., 183: 105, July 22, 1920. SUMMARY 6. ScoTr, Ann. of Int. Med., 5: 1028, May, 1921. 7. CLAWSON AND BELL, Arch. of Path., 4: 922, December, Seventy-four cases of cardiovascular syphilis 1927. form the basis of this report. The ratio between 8. PAULLIN, Trans. of the Ass. ofAm. Phys., 42: 217, 1927. males and females was 6.4 to 1. Sixty-four of 9. WARTHIN, Am. J. Obs. and Gyn., 15: 595, May, 1928. the patients were. white and 10 were coloured. 10. CoomBs, Bristol Med. Chir. J., 43: 1, 1926. The average age of all cases was 50 years, with 11. BROOKS, Am. J. of Syphilis, 5: 217, April, 1921. 12. KEEFER AND RESNIK, Arch. Int. Med., 37: 264, extremes between 32 and 74 years. About two- February, 1926. thirds of the cases occurred between 40 and 55 13. HORDER, The Lancet, 210: 695, April, 1926. years. The average interval between the primary 14. SCOTT AND SAPHIR, Trans. of the Ass. of Am. Ph s., infection and the onset of 42: 36, 1927. syphilitic symptoms 15. HOOVER, J. Am. M. Ass., 74: 226, January, 1920. was 24 years. The most frequent presenting 16. WARTHIN, Am. J. of Syphilis, 2: 425, July, 1918. symptom was dyspncea on exertion. Paroxysmal 17. OSLER AND MCRAE, Aortic Insufficiency. Principles and Practice of Medicine, D. Appleton & Co., New dyspncea is much more commonly associated York, p. 826, 1925. with marked cardiac enlargement than with 18. HICKEY, Personal communication.

THE BEROLOGICAL DIAGNOSIS OF UNDULANT FEVER.- 1 in 100, or 1 in 300. According to Kristensen a titre IEI. Meisel in Poland has examined the serum from 687 of 1 in 100 to Bang's bacillus is diagnostic of infection patients for agglutinins to Br. abortw; the serums were with this organism; but the author maintains that this sent to the laboratory for a Widal or a Weil-Felix test, criterion is liable to lead to errors of diagnosis. To The serums from two patients, each of whom was suffer- ascertain whether the positive results with Bang's ing clinically from undulant fever, agglutinated Bang's bacillus obtained with the serums of certain enteric and bacillus to a, titre of 1 in 800 'or X in 1000. Neither of patients were due to coagglutination the author these serums had any agglutinating action on the tested serums, prepared by inoculating animals with typhoid or paratyphoid A and B bacilli, or on B. typhoid or paratyphoid- bacilli or with Proteus X 19, protes X 19. On the other hand, among 167 serums against Br. abortw; no agglutination occurred. He agglutinating one or other members of the enteric group, therefore concludes that these results are not explicable there were five whieh at the same time agglutinated on the basis of coagglutination, but indicate rather that Br. abortuns to a titre of 1 in 50 or 1 in 100; and among the patients have at some previous time suffered from 186 serums agglutinating Proteue X 19 there were 11 undulant fever.-C. B. Soc. de Biologie, p. 534, June 6, which agglutinated Br. abortus to a titre of 1 in 50, 1930.