Analysis of the Acute Paroxysm
If we reflect on the general features and local characters of an initial outbreak of gout they are precisely such as would, did they occur anywhere but at the classic site, the big toe, suggest an infection. The abrupt onset, the local signs, the crisis, and no less the subsequent swift restoration to health, how strikingly reminiscent of an exanthematous fever! Moreover, does not this outward clinical resemblance seem to predicate an inward pathological similarity? And now to scrutinise more narrowly the component elements that make up the content of a paroxysm of gout.
Its fulminant onset, with shivering, if not a definite rigor, in a person in sound and sometimes exuberant health, irresistibly reminds one of the sudden onfall of an infective disorder. Doubtless, as Duckworth says, “the conditions leading up to the attack have been some time previously in operation.” But, as he rightly contends, “some determining factor must now be invoked to explain how, as it were, the train is fired.” Quite so, and what more likely to call into the open these latent morbid potentialities than an infection?
The constitutional disturbance is often profound, certainly out of all proportion to the severity and extent of the local phenomena. Especially prominent are the nervous concomitants—the excruciating pain, the irascibility, etc. Viewing these in light of the paroxysmal nature and periodicity of gout, Duckworth postulated a kinship between the disorder and the paroxysmal neuroses. But, given an infective element, what more plausible than to attribute the nervous phenomena of gout to the simultaneous action of its toxins on the higher centres?
The temperature curve, again, is obviously compatible with this conception. It begins abruptly, its course punctuated by daily remissions. No specific peculiarities apparently differentiate it from other arthritides of established or assumed infective origin, but its relatively low grade pyrexia recalls that typical of gonococcal arthritis. Its most striking feature, however, is the disproportion between the level of the pyrexia and the intensity of the general and local phenomena. Moreover, the temperature is not only low, but relatively ephemeral in duration, while the inflammatory reaction in its violence emulates that of the most sthenic forms of arthritis.
Albeit both the febrile disturbance and the local reaction display infinite grades of severity. Thus, acute gouty polyarthritis may be afebrile and the asthenic varieties of the affection marked by little inflammatory reaction. All these vagaries, however, are quite compatible with infection—the reflex, as it were, of varying degrees of toxæmia.
Says Duckworth, “The pyrexia proper to acute gout is paroxysmal with remission, and the pain of gout is likewise paroxysmal. One is reminded of the influence of marsh poison upon the nervous centres. This paroxysmal no less than periodic element in gout stamps a nervous character upon the malady and binds it in alliance with other well-recognised neuroses.”
How interesting these reflections by this distinguished physician in light of latter-day revelations! For, in so far as these features in gout are reminiscent of malaria, they disclose an affinity, not for a malady of nervous, but one of established infective, origin.
Simultaneously with the onset of pyrexia the pulse quickens. The blood shows that increase in fibrin characteristic of inflammation, a fact noted by Gulland, Cabot, Buchanan and others. But more significant is the presence of leucocytosis. It may be of high grade. In a case of acute gouty polyarthritis recently under my care the leucocyte count reached 27,000. Even in a subacute example of the classic monarticular type the leucocyte count attained 25,920. It was of leucoid type and attended by moderate anæmia due to deficiency of red corpuscles.
Nor is leucocytosis restricted to the periods of exacerbation, but it may be met with in the inter-paroxysmal stages. In my experience, even in cases of definitely chronic type it may reach 14,000. The higher grades of leucocytosis are obviously very suggestive of an infection, and that lesser degrees should be encountered in examples of definitely chronic type seems to point to gout being of the nature of a chronic or serial infection.
I would here add also that the converse of leucocytosis, viz., leucopenia, is sometimes met with in chronic cases. Dr. Munro and I have met with two instances of such in chronic gout in the intervals between paroxysms. This decrease in the number of leucocytes (leucopenia) is, of course, deeply interesting and, needless to say, quite compatible with infections, e.g., enteric, malaria, tuberculosis. In fact, it suggests that gout may be the outcome of divers infections, and not due to any specific organism.
Enlargement of the lymphatic glands was, by older authors, believed not to occur in gout. But obviously the lack of macroscopic evidence does not exclude the possibility of microscopic changes in these structures. The likelihood of such, moreover, is enhanced by the occasional occurrence of lymphangitis in connection with the inflammatory articular lesions. Buzzard, indeed, long since claimed that there was “clinical evidence of subacute gouty inflammation of lymph spaces in certain regions due to uratic deposit and influence.”
As a matter of fact, enlargement of the lymphatic glands does occur. Thus, my colleague James Lindsay cites an instance thereof. The subject, a painter, fifty-three years of age, had gout of some three years’ standing. During an acute paroxysm thereof “there was a mass of glands in the right groin, synchronous with an acute inflammation affecting the right knee and periarticular tissues. On the subsidence of the gouty inflammation the glands became smaller, but never entirely disappeared during the four weeks he was subsequently under observation.”
Splenic enlargement, states Duckworth, has been met with in many cases of gout, and occasionally infarcts. But such splenic enlargement is, he thinks, not specifically related to gout, but is due to associated conditions. Personally, I have not as yet met with splenic enlargement in gout.
This aside, is it not palpably significant of infection that Paget, Garrod, and others, repeatedly noted the incidence of acute phlebitis in a limb the seat of acute articular gout? Did we observe such a complication in any arthritis other than gouty, should we not inevitably regard it as indicative of the spread of an infection from the joint to the related veins?
Reverting to the local articular phenomena, they are not only compatible with, but emphatically suggestive of, an infective source. The typical signs of inflammatory reaction are swiftly installed in acute classical gout, and this with an intensity unrivalled save by the most sthenic types of acute arthritis. Witness how insistent were our forefathers, e.g., Scudamore, on the differentiation of acute gout, not so much from acute rheumatism as from erysipelas or phlegmon. Garrod, indeed, held that “if a medical man, by chance entirely ignorant of the nature of gout, were to see a toe affected by this disease in its full intensity, swollen, hot, red, and tender, he would probably think that the affection must of necessity terminate in suppuration, yet I believe this never happens as the result of simple gouty inflammation.” This leads us to note a salient feature of gouty inflammation, viz., it never results in pus formation. Now, allowing for the increased powers of discrimination that happily to-day are ours, is it not, I ask, significant that the disorders deemed most likely of confusion with acute gout belong to the frankly infective category?
That Garrod’s caveat was not uncalled for I feel sure, having myself known an acute gouty arthritis incised in the hope of evacuating pus. Sometimes the error in judgment is reversed and pyæmic or septic conditions in or near the great toe joint confounded with gout. Thus, Sir James Paget tells of an instance in which a pyæmic abscess forming near the great toe and consequent upon ligaturing of piles was thus confused. I recall, too, another example in which the supposed gouty arthritis of a great toe was of pyæmic nature, the outcome of a suppurating otitis media. Garrod, it may be recollected, ranked pyæmia as one of the disorders to which gouty subjects were especially liable.
Gouty inflammation resembles most other forms of the same morbid change, but some, however, contend that the association of œdema therewith is pathognomonic. Indeed, by some of the older authors this concomitant feature of gouty inflammation ranked as a criterion differentiating it from “true rheumatic inflammation.” Œdema, of course, is not distinctive of gouty as opposed to other forms of inflammation. But its occurrence therein is, we would submit, but another token of its affinity with the infective arthritides. We need but recall the constancy with which local œdema is met with in, e.g., gonococcal arthritis. More typical of gout, however, is the desquamation of the cuticule that follows the subsidence of the acute arthritis. Here we are reminded of the similar peeling of the skin that occurs in another infective disorder associated with arthritis, i.e., scarlatina.
Acute gout is definitely paroxysmal. The attack, at any rate when primary, is relatively ephemeral, lasts but a few days, and after it has passed, as Cullen says, “leaves the person in very perfect health, enjoying greater ease and alacrity in the functions of both body and mind than that for a long time before experienced.”
In short, acute gout would appear to be a self-delimited disease, its fleeting duration predicating that if an organism be responsible, the same is short-lived. Even in chronic gout, though it never quite loses its grip of those it has made its prey, yet nevertheless there are intervals of respite between the attacks, however long the latter may be. In other words, the disease never loses its paroxysmal character, which to my mind is very suggestive of a serial infection.
The periodicity of gout was, as we have seen, well known to the ancients. Its recurrence in early spring and late autumn has even been celebrated in verse:—
“On whose sacred internodial Altars I
Each Spring and Fall at least will sacrifice
Morbifick, painful loads of Matter tartarous,
With recrements of nervous juice impregnate.”
“The Honour of the Gout,” by Philander Misaurus.
Scudamore referred its prevalence at these particular seasons to their attendant vicissitudes of heat and cold (the strongest of all the exciting causes of gout). Trousseau states that “gout with successive paroxysms shows itself early or late in the year, at the beginning of spring or late autumn, the wherefore I know not.”
This tendency on the part of acute gout to seasonal rhythm is ultimately lost. For, once the disorder is established, no period of the year confers absolute immunity. Whatever be the explanation of the vernal and autumnal incidence of gout in its early stages, this peculiarity is at any rate not incompatible with its infective origin. In this connection it may be recalled that it was once described as “a tertian fever terminating in fourteen days.”
Again, further evidence may be obtained from the action of colchicum, our sheet-anchor in the treatment of gout. Thus, Dixon and Malden have shown that colchicine has no action on the metabolism of purins or on the kidney. On the other hand, it causes a primary diminution followed by a marked increase in the number of leucocytes, which suggests the possibility that it exerts its beneficial effects by combating infection.
Lastly, turning our attention to the anatomical changes as disclosed after death during an acute articular paroxysm, these present appearances quite compatible with their infective origin. Dr. Munro, in one of my examples of acute gouty polyarthritis, aspirated the knee joint. The results of cytological examination were precisely such as are deemed characteristic of arthritides of infective source.
The results of our analysis of the component elements of an acute paroxysm of gout are, for the following reasons, strongly indicative of the intrusion of an infective element:—
(1) The onset, temperature curve, the character of the local phenomena, and course of the disorder.
(2) The presence of leucocytosis with secondary anæmia, and exceptionally of leucopenia.
(3) Enlargement of the lymphatic glands, and possibly of the spleen.
(4) Occasional complication of the acute articular disorder by lymphangitis and phlebitis.
(5) The paroxysmal nature and periodicity of the disorder.
(6) The compatibility of the morbid anatomical changes and the cytological content of aspirated joint fluid with their genesis by infection.