The process is not a continuous, gradual ascent but takes place in attacks of exacerbations and remissions. Attacking first the distal portions of the vessels, it spreads upwards by involvement of other sections at different times.

The characteristic pathognomonic findings, suggesting infection as the exciting etiology, are multiple miliary abscesses or foci of giant cells, endothelial cells, leucocytes and disintegrated nuclei, lying in the periphery of a recent thrombus.

Unlike the pathologic anatomy, the pathologic physiology has been entirely neglected by all authors in describing the disease.

It is best studied on close observation of the local clinical phenomena, and appears to be as follows:

Early, there is a local anemia due to thrombotic obstruction of the arteries and to local vaso-spasm. At this stage, although there may also be some thrombosis in the veins, there seems to be sufficient collateral venous space to take care of the return of the lessened amount of incoming blood. Soon, however, the space for return flow is diminished, resulting in passive hyperemia in conjunction with the anemia. The venous blood extends into the capillaries giving a cyanotic appearance of the part, associated with coldness. The cyanosis and anemia are more easily seen by change in the position of the limb, adding the hydrostatic factor.

Due to deflection of the blood into the collateral arterial branches that spring from the arteries above the thrombus, and to the consequent increased pressure in those branches, there is developed an increased extent

of the capillary bed of these branches, giving increased rapidity of flow there with the resultant widening of the lumen of the arterioles and capillaries, increased thickening of their walls and growth in length, all of which constitutes work hypertrophy. In the meantime, the capillary beds belonging to the thrombosed vessels become congested due to passive venous stasis, undergo degenerative changes and rhexis and diapedesis results, with escape of blood into the tissues, which on oxidation gives the peculiar colorations observed in some sections of the affected parts.

In the later stages, if the thrombotic process is checked, and the collateral circulation established is more able to take care of the affected parts, local edema is seen, which at times becomes very marked. This is due mainly to the interference with the venous return but may also partly be due to increased secretion of the capillaries due to toxic irritation and also to the interference with the free flow of lymph caused by the same factor. That it is due partly to this irritation factor is proved by the fact that the amount of edema changes from time to time regardless of position of limb.

SYMPTOMS

The first manifestations, and ones that are often overlooked, are indefinite pains in the calf muscles, ankles, feet and toes. If the upper extremities are involved, similar pains occur in the hands, fingers and arms. These pains are considered, by those not familiar with the disease, as rheumatic or neuralgic or due to flatfootedness, and are treated as such. Other sensory and nutritional disturbances as

numbness, electric-shocks, burning, coldness and fatigue may accompany these pains. In many cases intermittent claudication occurs-the pains and other disturbances occurring on walking and disappearing with rest.

If examined at this stage we may find some trophic disturbances of the skin, muscles and other tissues. Impaired nail growth and small fissures and ulcers may be seen. The patient is often treated by the chiropodist for ingrown toe-nails or by the physician for an innocent ulceration when the underlying cause is this disease. On elevation of the limb ischemia is produced, while in the pendent position a bluish-red flush or congestion is seen, extending from the ankle to the toes, but especially pronounced in the latter location. There is an absence of, or a diminished pulsation in the dorsalis pedis, posterior tibials and, in extreme cases, even in the popliteals and femorals.

After some months or even years, ulceration and gangrene may set in, associated with excruciating local pain-pain that is not alleviated even by big doses of morphine. It is most severe at night, and peculiarly so, at certain hours. It has the nature of a cutting, tearing and boring associated with a burning sensation. Many a patient may attempt to commit suicide at this stage, to end suffering.

The gangrene and pain usually occurs in one or more of the toes, the big toe being more often involved. The duration of the pain is many weeks to months, except for occasional remissions for hours or days, when a dull ache is left behind.

months or years may follow this active stage. This period is characterized by the manifestations observed in the early stages of the disease, which may be somewhat accentuated.

The laboratory findings may be normal except for an erythrocytosis, a decreased coagulation time and a somewhat higher than normal blood sugar curve. All of these findings suggest greater concentration of the blood which, associated with the clinical appearance of a moderate anaemia, suggest a decreased total volume of blood. The blood pressure is always low, accounted for partly by this decreased volume.

DIAGNOSIS

The occurrence of the above symptoms in young persons in whom arterio-sclerosis is not marked or is not demonstrable; the absence of a syphilitic history and findings; the characteristic periods of exacerbations and remissions; the peculiar pains, the visible anemia associated with the blood findings, and the absence of pulsations in some of the arteries, make this disease a diagnostic clinical entity.

PROGNOSIS

Many of the cases end in the loss of a limb or limbs. Occasionally infectious, spreading gangrene may set in, resulting in death. A great many cases are comparatively free from distressing symptoms for periods of many months or years and enjoy fair health and comfort.

1 Laboratory determinations done by

TREATMENT

Various methods of treatment have been suggested and practiced with apparent success reported by enthusiasts. The relief offered and the supposed checking of the diseased process by the various methods practiced is no doubt due, in the majority of cases, to the natural remissions seen even if no treatment is instituted.

The methods employed are surgical, medical and vaccine injections. Of these, the surgical procedures, except in cases of amputation where it is imminent, are not only unsuccessful but actually harmful.

The most dangerous surgical procedure, one which met with greatest failure and resulted in many deaths, is that known as arterio-venous anastomosis. It consists of suturing the proximal end of the cut femoral artery to the distal end of the cut femoral vein in an attempt to fill the tissues with blood through the venous system. The irrational nature of this method is seen if we realize that the veins as well as the arteries share in the thrombotic occlusion. Goodman reviewed the records of 136 cases subjected to this procedure and found that of this number 30 died after operation, 11 more died after amputation and 45 required early amputation.

Another procedure is that of exposing the nerves and injecting absolute alcohol in it, suggested and practiced by Gilbert on some cases. This, however, does not treat the disease but only may afford the relief of pain. Besides, it has a limited application and may predispose to secondary infection.

A third surgical method used is femoral vein ligation in an "attempt

to bathe the tissues with blood." The fallacy of this is seen if we realize that this produces only more stagnation, predisposing to more thrombosis.

Amputation is a fourth surgical procedure resorted to probably more often than it should be. Many a limb would have been saved if more conservatism would be practiced. I have in mind 2 cases that were advised amputation by some eminent surgeons years before. They refused to submit to operation and are at present enjoying their limbs with comfort.

Of the conservative methods of treatment may be mentioned Bier's hyperemic suction, practiced by Sinkowitz and Gottlieb; intravenous injections of sodium citrate solutions, by Steel; typhoid vaccine injections by Goodman and Gottesman; autogenous vaccine injections, by Rabinowitz. Of these, the Bier treatment may be of value in selected cases. The intravenous citrate injection is rational for its anticoagulative properties but is objectionable for its pain and discomfort. Besides, the amount of fluid that can be given by this route is necessarily limited. The typhoid vaccine I found to relieve pain in one case in which I tried it, and the autogenous vaccine may do the same. It is doubtful, though, if any vaccine used by itself will effectively treat a chronic disease exhibiting such extensive pathology. At best it may check the further progress of the disease, but to overcome the chronic pathological process other means, directed towards that end, must be employed.

I am indebted to Dr. Willy Meyer for having demonstrated to me, on 2

of my patients, the method and value of the modified Kogo treatment, by duodenal flushing. I followed this method on 6 of my cases with good results in 5 and with uncertain results in 1 case which was far advanced in the disease.

The method consists in introducing the Rehfus tube into the duodenum and leaving it there for periods of three to four weeks. Through this tube 6 to 12 quarts of Ringer's solution is given daily. I found that normal sodium chloride solution or even plain water is just as efficacious in some cases. The amount of fluid to be given is to be measured by the ability of the cardio-vascular and renal systems to handle it.

Besides this abundance of fluid, dry heat by electric cradle is applied to the affected parts as often and for as long as the patient can stand it with comfort, care being taken not to produce any burns. Potassium iodide, 30 to 60 grains or more, is given daily in divided doses.

I use, in addition, local massage, elevation and lowering of the limb, and treat the patient constitutionally according to indication. To overcome

the marked insomnia and extreme nervousness of the patient, bromides, luminal, barbital and an occasional dose of morphine is of help. Smoking must be strictly interdicted.

The effects of this treatment are the allaying of pain, the return of function in the involved extremity, the falling off of any gangrenous part, and the healing of the resultant stump by normal healthy granulation. In one early case there was a return of the lost pulsation in the posterior tibial artery.

The rationale of this treatment is readily seen. The abundance of fluids given decreases the viscosity of the blood, dilutes the toxins, helps elimination of waste products and discourages further thrombosis by accelerating the rate of flow of the blood. The other methods employed encourage the formation of a collateral circulation and relieve stagnation.

The best results are obtained in the early stages, and if we would learn to recognize the disease in its very earliest stage and administer these treatments, a great deal would be done in the alleviation of suffering and in the prevention of debility.

MEYER, WILLY: Further contribution to the etiology of thrombo-angiitis obliterans. Med. Rec., March 13, 1920, xcvii, 425.

RABINOWITZ, H. M.: Experiment on infec

tious origin of thrombo-angiitis obliterans and isolation of a specific organism from the blood stream. Surg., Gyncol., and Obstet., September, 1923, Xxxvii, 353-360.

BUERGER, L.: Thrombo-angiitis obliterans:

A study of the vascular lesions leading to presenile, spontaneous gangrene. Amer. Jour. Med. Sci., 1908, cxxxvi, 567.

GILBERT, S.: New method of treatment of thrombo-angiitis obliterans. Jour.

Amer. Med. Assoc., 1922, lxxix, 1765. SINKOWITZ, S. J., AND GOTTLIEB, I.: Conservative treatment by Bier's hyperemic suction apparatus. Jour. Amer. Med. Assoc., March 31, 1917, lxviii, 961. STEEL, W. A.: Sodium citrate treatment.

Jour. Amer. Med. Assoc., February 12, 1921, lxxvi, 429. GOODMAN, C., AND GOTTESMAN, J.: Pain and its treatment in thrombo-angiitis obliterans. N. Y. Med. Jour., June 20, 1923, cxvii, 794. GINSBERG, N.: Peripheral gangrene due to treatment with reference to femoral vein ligation and sodium citrate injection. Amer. Jour. Med. Sci., September, 1917, cliv, 328.