Peripheral Vascular Disturbances
Thromboangiitis 0bliterans, Arteriosclerosis, and Arterial Thrombosis and Embolism
Norman E. Freeman, M. D.
Thromboangiitis obliterans affected a small proportion of the patients admitted to the vascular centers established in the Zone of Interior hospitals during World War II.Thromboangiitis as encountered in the Army did not differ materially from the disease as observed in civilian practice except that it was usually observed in earlier stages; very few instances of longstanding involvement were seen.
Analysis of Data
Of the 3,778 patients with vascular conditions observed at the vascular centers during World War II, 274 had thromboangiitis obliterans; percentagewise an incidence of 7.3 percent.All reported cases occurred in males.Of the 274 patients observed in the vascular centers detailed information was available for analysis on only 152 patients. In these 152 patients the great majority (122 patients) were in the age group between 26 and 40 years. The relatively low incidence (30 patients) under 26 years of age can probably be explained by the fact that the disease, although present in other soldiers in that age group, had not advanced sufficiently to produce symptoms.
As originally described (see Chapter II), the disease occurred in disproportionately large numbers among Jews. Information as to race was recorded in only 150 of the 152 in this series but in the 150 the distribution was as follows: 7 Negroes, 111 Caucasians, and 32 Caucasians of the Jewish faith.
Symptomatologyand Clinical Course
As mentioned previously, very few cases of longstanding involvement were seen in the vascular centers. The range in a group of 53 patients observed at Ashford General Hospital may be considered as typical. In this group the duration of symptoms ranged from 1 month to 13 years, but averaged only about 22 months.
The distribution of symptoms presented at the time of the patients’ admittance to the vascular centers was approximately the same as reported in other statistical surveys.Intermittent claudication, which Homans 1 has
1 Homans, J.:Circulatory deficiency in the extremities in relation to medico-legalproblems; arterioscleroticdeficiency (including diabetes); thromboangiitis obliterans, orBueger's disease. Ann. Int. Med.18:518-534, Apr1943.
termed "the one characteristic early evidenceof the disorder," was the most frequent complaintand was observed in 67 percent of the 152 patients in this series. Itwas usually associated withpain in the foot and leg. Sixty percent of the patients complained ofsome form of pain in theextremities and 20 percent of some disturbance of sensation, chieflynumbness on walking.Temperature differences, either subjective or objective, were observedin 45 percent of thepatients and migratory phlebitis in slighly less than a third.Ulceration was already present in 20percent of the patients when they were first seen, though gangrene wasunusual and wasobserved in only 4.4 percent of the patients. Nine patients hadvasomotor disturbancescharacteristic of Raynaud's phenomenon.
Although the clinical manifestations of thromboangiitis obliterans were usually most noticeable in a single extremity, the disease is a systemic vascular disorder and careful examination frequently revealed that the blood vessels of other extremities were also affected. In almost two-thirds (65 percent) of the 152 patients, 2 or more extremities were involved, and in 13 patients all 4 limbs were affected.
Despite the widespread character of the involvement, visceral manifestations were unusual. In 3 patients attacks of precordial pain suggested the presence of disease of the coronary arteries. In 1 patient, who had suffered from thromboangiitis obliterans of the peripheral arteries for many years, quadriplegia and other neurologic manifestations developed while he was under observation. His clinical course indicated that the cerebral vessels had also become involved.
In addition to a complete history and physical examination with particular attention paid to clinical evidence of vascular disturbances, certain special procedures were employed to establish the diagnosis of thromboangiitis obliterans. These were particularly necessary and of particular importance in a few patients who had been under examination and treatment on a variety of diagnoses in several installations before the correct diagnosis was made in one of the vascular centers.
The special procedures used to aid in the diagnosis of thromboangiitis obliterans included the accurate measurement of skin temperatures, oscillometric recordings of the peripheral arteries, arteriography, and biopsy studies. Constant temperature rooms were available at all of the vascular centers and were used to study the effect of varied degrees of coldness and warmth upon the skin temperatures of patients with thromboangiitis obliterans. In addition, skin temperature measurement and oscillometric readings were made before and after release of vasomotor tone by reflex vasodilatation, paravertebral injection of procaine, spinal analgesia, and peripheral nerve block. These procedures proved especially valuable in disclosing early involvement of small vessels as well as in the selection of appropriate patients for sympathectomy
and were used in all patients indicated. Arteriograms (thorotrast wasthe contrast medium used)were made in 4 patients in whom arterial involvement was suspected butnot confirmed by otherdiagnostic procedures. Peripheral pulses were normally present in eachof the 4, butarteriography demonstrated that the circulation was maintained by meansof collaterals. In 4other patients the diagnosis was substantiated by biopsy of theaffected vessels.
Various forms of nonoperative and operative treatment were employed in the management of patients with thromboangiitis obliterans at the vascular centers in the Zone of Interior during World War II. It was generally agreed, however, that no type of treatment was effective unless the patient stopped smoking.
Nonoperative Treatment. Ever since Erb 2 first called attention to the close relationship between smoking and endarteritis, this aspect of the problem of thromboangiitis obliterans has been the subject of numerous clinical and scientific observations. Silbert, 3 in an experience which covered 1,400 patients, observed no instance of the disease in a patient who had never used tobacco. Furthermore, he observed no instance of progression in 100 patients with the disease who gave up smoking completely and who were followed for over 10 years. He concluded, therefore, that thromboangiitis obliterans was caused by smoking in individuals constitutionally sensitive to tobacco.Horton, 4 on the other hand, found thromboangiitis obliterans present in 68 of 948 nonsmokers. His position was that while there was no question that smoking had a decidedly bad influence upon the course of the disease, it did not necessarily follow that smoking was a cause.
Whatever may be the etiologic relationship between tobacco and thromboangiitis obliterans, it is generally agreed that abstinence from smoking is a mandatory part of therapy. Allen 5 regarded it as "largely useless" to treat patients who continue to use tobacco and Homans 6 said of the patient, "Above all, if he will not abandon tobacco smoking, his disease will almost necessarily persist and indeed will probably be aggravated."
It is known that only 4 of the 274 patients with thromboangiitis obliterans observed at the 3 vascular centers did not smoke. Information about their subsequent habits, after they had been warned to discontinue smoking, was obtained for 93 of these patients. Seventy-seven had stopped smoking entirely, and persistence of the symptoms was observed in only 2 patients in this group. Among the 16 who had continued to smoke, progression of the vascular obliteration was observed in 8 during the period covered by this investigation.
2 Erb, W.: Ueber Dysbasia angiosclerotica, intermittierendes Hinken. München. med. Wchnschr. 51: 905-908,1904.
3 Silbert,S.: Etiology of thromboangiitis obliterans. J.A.M.A. 129: 5-9, 1 Sep 45.
4 Horton, B.T.- Outlook in thrombo-angiitis obliterans. J.A.M.A. 111: 2184-2189, 10Dec 38.
5 Allen, E.V.: Thrombo-angiitis obliterans. Bull. New York Acad. Med. 18: 165-189,Mar 1942. 6 See footnote 1,p. 375.
The opinion of the officers who directed the study and treatment of the patients with thromboangiitis in the vascular centers might well be summarized.
Capt. J. W. Kahn in writing of the experience at Ashford General Hospital reported that while smoking is not the cause of thromboangiitis obliterans, it is a very aggravating factor. Unless the patient stops smoking completely, no form of treatment, including sympathectomy, is of benefit. Recurrent migratory phlebitis has disappeared with the cessation of the tobacco habit alone. Wounds and gangrenous areas have cleared rapidly and pain has considerably improved when the patient stopped smoking. Following sympathectomy patients who still smoked complained of pain, but the pain was quickly relieved thereafter when the patient abstained. Gangrenous areas were slow in healing and demarcating when the use of tobacco was continued after sympathectomy, but gratifying results were noted when the smoking was stopped.
Maj. David I. Abramson in writing of the experience at Mayo General Hospital stated that it was felt at this center that no medication would be of any value if the patient did not abstain from smoking. When the diagnosis of thromboangiitis obliterans was made, the nature of the disease was thoroughly discussed with the patient, and the dangers of continuing to smoke were graphically illustrated by showing him the extremities of patients in an advanced stage of the disease. Most of the patients when informed of the relationship of smoking to the progress of the disease stated that they would abstain completely. However, in a number of instances it was subsequently brought to our attention that they had been unable to abide by their pledge.
At the vascular center of DeWitt General Hospital the inability of some men to abstain from the use of tobacco was recognized as a problem and was so studied. Silbert 7 called attention to the " . . . extraordinary fact that some men will not stop smoking even when repeatedly warned that failure to do so will result in the loss of their extremities."Many of the patients seen at this center had previously passed through several medical installations. When the diagnosis of vascular disease was first suspected, most of them had been told by the medical officer that they "should stop smoking" or "should cut down on smoking," but the importance of complete and permanent abstinence from tobacco had never been stressed to them. In many instances the story was the same: The patient resolved to stop smoking and did stop temporarily, but resumed the habit. With each successive resolution and failure the process of stopping became more difficult.
Rather than adopt a defeatist attitude toward the problem, a policy was developed at the vascular center of DeWitt General Hospital in which each patient was permitted to decide the matter for himself. This plan was based on Homans' suggestion 8 that "the individual should know that he will never
7 Silbert, S.: Treatment of thrombo-angiitis obliterans. Hebrew M. J. 1:135-149, 1942.
8 Homans, John: Circulatory Diseases of the Extremities. New York, The Macmillan Company, 1939.
smoke again." To accomplish this result each patient withthromboangiitis obliterans wasinstructed to continue smoking until he had realized two things: (1)that the diagnosis ofthromboangiitis was irrefutable, and (2) that after considering thematter thoroughly andcompletely he had come to know he would never smoke again.
The patient must have no doubt about the validity of the diagnosis, and he must be convinced in his own mind that abstinence is the only solution to his problem. Time is required for the patient to arrive at this state of mind, but it was the experience at DeWitt that as soon as it was accomplished the soldier quickly adapted himself to the inevitable. Investigation showed also that the first time the patient stopped smoking was the one time he was most likely to succeed.
The patients were helped by being segregatedinto a nonsmoking ward where they were givenspecial privileges. During the early period of total abstinence it wasfound helpful to use groupsuggestion, occupational therapy, and sedation. Much, of course,depended upon the personalrelationship between patient and medical officer.
Under the aggressive policy outlined, the proportion of patients who succeeded in stopping smoking was greatly increased. In 39 successive cases there were only 2 failures. Horton 9 has estimated that of those who do stop smoking 50 percent relapse, and it is realized that many of the patients who succeeded in stopping while at the vascular center may have returned to the habit after separation from the service and were doomed.
Provided the patient had stopped smoking, typhoid vaccine gave excellent results. The rationale of the use of typhoid vaccine is primarily the production of maximal vasodilatation as the result of the febrile reaction .The vaccine was administered intravenously and the dose was individualized in each patient so as to produce a febrile reaction up to 102° F. without causing a chill.
The injection of tissue extracts improved the ability to walk in about half of the patients. Various pancreatic tissue extracts, including padutin and depropanex, were used by the intramuscular route. While intermittent claudication was relieved in many of the patients by the use of these extracts, other features of the disease were not affected.
Only indifferent results were secured by the use of Buerger's postural exercises and physiotherapy, including intermittent suction and pressure, and intermittent venous occlusion, though they were employed in numerous cases.
Operative Treatment. Sympathectomy was performed for involvement of 1 extremity in 33 of the 152 patients in this series, and for 2 extremities in 18. In 2 patients 3 extremities were affected and sympathectomy was performed. The indications as well as the results, which were generally good, are discussed in detail in the section on sympathectomy in Chapter XVI.
9 Seefootnote 4, p. 377
In 12 patients treatment consisted in repeated blocking of the lumbar sympathetic ganglia with procaine. Crushing of the peripheral nerves for the relief of intractable pain was employed in only 2 patients.
In only 3 of the 274 patients in this series was major amputation of an extremity a necessity. However, only 24 recovered sufficiently to continue in the service; 3 returned to general duty and 21 to limited duty. The remainder were separated from the service by retirement or by Certificate of Disability Discharge.
It has been noted that thromboangiitis obliterans was observed in the vascular centers in World War II chiefly in the early stages of the disease. This may be explained by the fact that men suffering from clear-cut disorders of the peripheral circulation were rejected at the original physical examination; Jahsman and coworkers 10 reported on the recognition of the disease in young draftees. It therefore seems probable that in most instances the disease developed during the time the patient was in the service. No evidence was obtained, however, that military service aggravated a preexisting disorder.
The fact that in 274 patients only 3 had to have major amputations of extremities, casts a hopeful light upon the therapy of thromboangiitis. The success can largely be attributed to the awareness by medical officers of the problem of vascular disorders which made early recognition possible, and the existence of specialized vascular centers staffed by experts and equipped to provide any therapeutic measures prescribed.
Arteriosclerosis of the peripheral vessels sufficient to produce symptoms of vascular disturbances was reported in 55 patients from the 3 vascular centers in the Zone of Interior. The number is small but the incidence, in view of the age distribution of the personnel in the Army, is surprising. Although many observers believe that when arteriosclerosis is invoked as a cause of circulatory disorder the diagnosis should be looked upon with doubt if made upon individuals under 60 years of age, there was in the present series but 1 patient beyond that limit.The majority of patients fell into the age group 40 to 55 years. The youngest patient in the series was 30 and the average age was 45 years.
In more than half of the patients both lower extremities were affected. One lower extremity was involved in 6 patients and the upper extremities in 8. Intermittent claudication was present in 2 7 patients when they were first seen. Twenty complained of pain and 11 of abnormal coldness of the extremi-
10 Jahsman, W.E.; Durham, R.H., and Dallis, N.P.: Recognition of incipient thromboangiitis obliterans in young draftees. Ann. Int. Med. 18:164-176, Feb 1943.
ties. A number presented evidence of systemicvascular disorders. Ten had cardiac disease, 5hypertension, 3 diabetes, and 1 nephritis.
Skin temperature determinations and oscillometric readings were useful in establishing the diagnosis of arterial insufficiency. Measurements of skin temperature after reflex vasodilatation or blockage of the vasoconstrictor impulses were made in 6 patients.
Special attention was paid to evidences of calcification as revealed by roentgenograms of the extremities. Calcification was observed in all the cases reported from the vascular center of Ashford General Hospital and in two-thirds of the patients reported from the other centers.
In this connection it was observed at Ashford that the incidence of calcification of the peripheral blood vessels in males between the ages of 30 and 40 years of age was remarkable. Capt. J. W. Kahn of this center reported on 10 patients in this age group who were sent to this hospital between March 1944 and September 1945 for vascular study because roentgenograms revealed calcification of peripheral blood vessels. Roentgenograms had been made for reasons other than vascular disease or vascular complaints and calcification was discovered accidentally. None of the patients in this group had any subjective signs of vascular incapacity nor, upon intensive vascular study, could they be found to have any objective signs of either organic or vasomotor disease. Oscillometric readings, skin temperature readings, and vasomotor tests were well within normal limits. None of the roentgenograms in this group revealed the spotty, mottled type of calcification; all showed smooth uniform shadows gradually fading into normal vessels proximally.
According to Captain Kahn, these findings are in keeping with the research of Huyler who studied calcification in a large series of patients for a number of insurance companies.The result of this research had revealed that those with the smooth type of calcification were relatively symptom-free as compared with those with the mottled type.
While none of the roentgenograms of the 10 patients revealed the spotty, mottled type, a number of the patients with firm, palpable, noncompressible, cord-like peripheral arteries failed to reveal any evidence of calcification. These patients, however, had other stigmata of generalized arteriosclerosis; the age group was higher and their symptoms were referable to cardiovascularrenal degenerative disease. The possibility of generalized atheromatous disease, without visible calcification, suggested to Captain Kahn a form of medial sclerosis of the Monckeberg type.
It is well known that calcification in arteries can be shown by roentgenogram in only 35 to 40 percent of the patients with sclerotic disease. There is no question that relatively young patients presenting such findings will exhibit evidence of this disease at an earlier age than those in whom no evidence of calcification is found.
Therapy and Disposition
Lumbar sympathectomy was performed in 4 of the 55 patients, with satisfactory results in all. Other forms of treatment such as intramuscular injections of depropanex, intermittent venous occlusion, and physiotherapy were employed in a small number of patients. No major amputations were necessary, and only 1 minor amputation was performed.
Five patients were returned to limited duty. The remainder were separated from the service.
ARTERIAL THROMBOSIS AND EMBOLISM
There were 18 cases of spontaneous arterial thrombosis of unknown etiology reported from the 3 vascular centers. Case histories are not available to permit analysis.
There were 6 instances of embolism of the peripheral arteries reported from the vascular centers. Case histories are available for only 3 patients. In 2 of the 3, femoral embolism was followed by gangrene of the leg and amputa tion was necessary. The third patient had been successfully treated in an overseas hospital by embolectomy of the popliteal artery. When he was examined at one of the vascular centers, the pulses were found to be normal.