Brit. 07. Dis. Chest (I959) 5:t, 52.

THE PROGNOSIS IN SYPHILITIC AORTIC ANEURYSM AFTER TREATMENT WITH PENICILLIN

BY RICHARD WARD AND LUCIEN READ

From the Blackburn Royal Infirmary, Lancs.

THE prognosis of patients suffering from syphilitic aortic aneurysm, although varying widely and being influenced by occupation and age of onset, is undoubtedly very poor. Kampmeier (1938) stated that, with comparatively few exceptions, the duration of life after the onset of symptoms in aneurysm of the aorta was to be measured in months. Grimble (I955) , in a review of patients with cardio-vascular syphilis treated in the days prior to penicillin, showed that arsenic roughly doubled the expectation of life; in a selected group of patients untreated the duration of life averaged 15.6 months from the onset of symptoms. I t was natural, therefore, that attempts by surgical means should be made to eliminate one of the major causes of death in these cases, namely rupture of a saccular aneurysm. For example, Borrie and Griffen (I 95 o) used Colt's umbrella in nine cases; of these four died within the following sixteen months. Successful resection of saccular aneurysms has been accomplished on a number of occasions. Bahnson (I954) operated upon eleven patients. The operations were technically difficult and in five only was a satisfactory result obtained.

There have been few accounts of the effect of penicillin on the prognosis in this disease; Moore (I949) in treating six cases of saccular aneurysm did not have encouraging results, since, of these, two ruptured within six months of completing treatment. O'Brien et al. (1955) treated five cases of saccular aneurysm with penicillin and four o f these were alive at the end of a five-year follow-up. They concluded that penicillin may have been more effective than metal therapy in halting the syphilitic process and prolonging life.

It is the object of this paper to discuss thirteen cases of syphilitic aortic aneurysm treated with penicillin.

MATERIAL

This small group comprised seven females and six males, who had been observed tbr periods between 20 and 74 months. Their ages varied between 55 and 73 years. There were nine saccular and four fusiform aneurysms, and all patients had positive serological reactions for syphilis. It is not intended to discuss in detail the symptomatology except to emphasise that all patients when referred to us were definitely symptomatic. Pain, dysphagia and hoarseness were the most common complaints. The diagnosis was always easy to make with the aid of X-ray screen examination and films. It is interesting to note that two patients presented with superior vena caval obstruction and

(Received for publication July 3 o, 1958.)

pRoGNOSIS IN SYPHILITIC AORTIC ANEURYSNI AFTER TREATMENT WITH PENICILLIN 5 3

remain well at the time of writing this report. Coincident aortic regurgitation was present in four cases, and three showed evidence of neurosyphilis.

TREATMENT

No case had received any therapy prior to coming under our care. The earlier patients were given potassium iodide in a dosage of 60 gr. daily for three weeks before starting treatment with penicillin. Soon this was given up, as there appeared to be little evidence that it had any effect on syphilitic lesions with the exception of cutaneous gummata. Each patient, therefore, received a daily injection of 600,000 units of procaine penicillin until a total of 3o mega units had been given. This constituted the complete treatment and the course was not repeated.

HERXHEIMER REAGTIONS

Two patients had Herxheimer reactions, cases 2 and 4. In each there was a sudden " collapse " with fall of blood pressure and associated weakness. Both patients recovered in a few hours. Subsequent electrocardiography did not show any evidence of myocardial infarction and treatment with penicillin was continued the next day. It appears that this reaction is of the " all or none" type (Bull. World Health Organisation, 1954, quoted by Lancet leading article, 1954, and Moore et al., 1949) , and that there is, therefore, no valid reason for starting treatment in these cases with a dose of penicillin which is therapeutically inadequate. The available clinical and experimental evidence (Sheldon et al., 1952) still points to the Herxheimer reaction as being a hypersensitivity response.

RESULTS

Of the thirteen cases treated, three have died during the follow-up period, none as a result of rupture of the aneurysm (see table). Two of these patients were amongst the oldest in the group and the third had aort ic regurgitation. Of the others, nine are leading relatively normal lives, and one is subject to attacks of left ventricular failure. After treatment, there was complete relief of pain (five cases in which it was present), in all cases a feeling of well-being, improvement in phonation, disappearance of dysphagia and cessation of hmmoptyses. In six cases there was a great gain in weight necessitating considerable restriction of food intake later. There was no change in the signs of superior vena caval obstruction (two cases). In some we have noted the occurrence of pulsation in the wall of the aneurysm when it had not been present before treatment. In Case I there was rapid and considerable increase in size of the aneurysm, but although he died 2o months after completion of treatment, death was, according to his general practitioner, due to bronchitis and heart failure and not to rupture. The saccular aneurysm present in Case 2 also increased in size (see Case Report), but the patient has remained free from his original complaint of left upper chest pain and leads an active life. There was no alteration in the serological tests following therapy in any case.

54 WARD AND READ

TABLE OF CASES

Case Age on aVo. diagnosis

x 70

2 60 3 65 4 65

5 74 6 64

7 58 8 58

9 63

Io 61

xl 73 I2 57

13 55

Saccular Se~ OY

fusiform

M S

M S F F F S

F F M S

M F F S

M F

F S

M S F S

F S

Observation after therapy

(months)

20

52 32 35

26 64

32 35

65

74

68 60

48

Comment

Died, according to general practitionel from bronchitis and heart failure.

Normal life but not at work. Attacks of bronchitis. Getting about well despite great gain ir

weight. Dieting. Died. Was working as bookmaker's runner fore

years after diagnosis and treatment Aortic regurgitation present.

Walking two miles; swallowing improved Carcinoma of colon removed one yeal

after completion of treatment. Reason. ably well and enjoying an active life.

Incipient left ventricular failure. Aorti, regurgitation.

Ovarian cyst removed without inciden three years after treatment. Aorti regurgitation.

Able to walk 2 miles. Does all house work and cares for invaliq

husband. Died four years after diagnosis and treat

merit from bronchopneumonia. Aorti, regurgitation.

I l l u s t r a t i v e C a s e H i s t o r i e s

CASE 2. A 6o-year-old m a n employed by the corporat ion, loading dustbins and driving a horse wagon, was referred in November r953, complaining o f a dull aching pa in in the left shoulder and uppe r par t of the left chest at the back and front, present for five months. In addit ion, he had had an occasional feeling of faintness dur ing the preceding five years. Clinical examina t ion showed a thin, heal thy-looking man, with systolic pulsation in the second left interspace and benea th the th i rd left r ib close to the s ternum. Aortic second sound loud and " r inging." B.P. i3o/7o , no aort ic regurgi tat ion. Th e re was no clinical evidence of neurosyphilis. W.R . and K a h n were strongly positive. Screening did not show any pulsation of the wall of the aneurysm. (Figs. x and ~.)*

Treatment and Progress. H e was admi t ted to hospital, t rea ted with penicillin and had a mild He rxhe imer reaction. By J a n u a r y I95 4 he was free f rom pa in and screening showed slight pulsation in the wall o f the aneurysm. One year la ter he had gained a stone in weight and was symptom free. In i956 the sternal pulsat ion was more marked, bu t apar t f rom some attacks of faintness he was well. Increased size of the aneurysm is shown four years after t rea tment . (Fig. 3.)

* The figures referred to in the text appear on Plate IX.

PLATE I X

Fig. i . --Case 2. Postero anterior view. November, I953.

FIC. 2.--Lateral view.

FIG. 3.--Case 2. December, i957. FIG. 4.--Case 4.

PROGNOSIS IN SYPHILITIC AORTIC ANEURYSM AFTER TREATMENT WITH PENICILLIN 5 5

CASE 4. In March i955 this 67-year-old woman was referred by a colleague in the E.N.T. department to one of us. For two months she had felt exhausted, breathless, had difficulty in swallowing and had a brassy cough. On examina- tion she looked ill, had pale mucos~e, non-pulsatile distension of the external jugular veins and fullness of the lower part of the neck. B.P. 2oo/I IO; pulsation in the second and third right interspaces. Left pupil smaller than right, both irregular and with sluggish reaction to light. W.R. and Kahn strongly positive. Investigations in hospital showed the C.S.F.W.R. to be positive with luetic type of Lange curve. Both vocal cords moved normally. On barium swallow there was considerable delay in the oesophagus, caused by external pressure from the aneurysm (Fig. 4) whose right border showed slight pulsation. She received 20 mega units of penicillin. (Herxheimer reaction occurred.)

Progress. One year later she was able to swallow anything and had gained 2 stone, but despite this her dyspncea was less. Strict dieting started. In June 1957 barium swallow did not show any delay, the aneurysm was no larger and no pulsation was visible. In September i957 she was leading a fairly normal life and able to go to a neighbouring holiday resort for day excursions, having reduced her weight by I½ stone. No change at time of writing.

Discussion We believe from our admittedly small experience that penicillin relieves

many of the symptoms of patients suffering from syphilitic aortic aneurysm. The improvement in the general condition of the patients and the gain in weight noted in several cases bears out the assumption of Curtis et al. (I95I) that occult lesions are present elsewhere than in the cardiovascular system in these cases. The Treponema paltidum is extremely sensitive to the action of penicillin and true resistance to this antibiotic does not develop (Beerman et al., I950 ). It is probable that the disappearance of syphilitic granulation tissue from the aorta takes many months and that little happens to the lesions during actual treatment. Sinclair et al. (I954) , reviewing the histology of patients dying following treatment with penicillin for cardiovascular syphilis, although not stating the causes of death, found that in those treated up to four weeks before death there were severe inflammatory changes present in the aortic wall. In those dying ten weeks or longer after treatment there was a marked decrease in or absence of lymphocytic or plasma cell infiltration. In agreement with these findings it is our experience clinically that relief of pain, when present, occurred in under six weeks, but that there was a continued improvement in the general condition of the patient for many months, even up to one year, after the completion of treatment. As regards the h~emoptyses, it is difficult to understand why penicillin therapy should lead to their cessation. These were a leading symptom in three cases. In Case I during treatment a h~emoptysis of almost I pint occurred. He survived for 2o months despite this and it was thought that the blood had come from the aneurysm via the left main bronchus. In two other cases it was merely staining of the sputum and believed to be in some way due to pressure from the aneurysm on the bronchial wall.

Penicillin has thus been shown to have a marked effect on the Treponema

56 WARD AND REAl)

pallidum and syphilitic granulation tissue. I t would appear to us that this beneficial effect may mitigate against rupture of the aneurysmal wall.

I t is probable that many saccular aneurysms are present a long time before, by reason of their pressure effects, they become evident. The prognosis may, therefore, not be quite as gloomy as is generally supposed. Nevertheless it is certainly bad and, despite the ingenious means devised by our surgical colleagues, operation, often in an elderly subject, is extremely hazardous. I t appears to us, therefore, that surgery will have no further part to play in the treatment of this condition and that in many cases penicillin will relieve symptoms and improve the prognosis.

S u m m a r y

Thirteen cases of syphilitic aortic aneurysm have been treated with penicillin. All had, on diagnosis, definite symptoms which suggested that death might occur within one or two years. Nine patients are leading reasonably normal lives, having been observed for varying periods between 32 and 74 months.

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SHAFF~R, L., and WILE, U. (I95I):J. Amer. Meal. Ass., x45 , 1223. GRIMBLE, A. (I955): Guy's Hosp. Rep., IO4, 239. KAlVlPMEIER, R. H. (1938): Ann. Int. Med., x2, 624. Lancet, leading article (1954) : 2, i268. MOORE, J. E. (1949) : Amer. o7. Syph., 33, 43. O'BRIEN, J. F., SMITH, C. A., and FISHKELLER, M. A. (I955) : Brit. o7. yen. Dis., 3x, 74- SHELDON, W., HE'ZMAN, A., and EVANS, L. (1952): Amer. J. Syph., 36, 77. SINCLAIR, H. A., and WEBSTER, B. (I954):Amer. 07. Syph., 38, 54.