Summary
It now devolves upon us to decide whether the phenomena of gout are best explicable as the outcome of auto-intoxication, or of infection or sub-infection. The uric acid theory was in truth one of auto-toxæmia, the varied manifestations of gout being attributed to mechanical or toxic irritation by uric acid, the end-product of purin metabolism. But, as we hope to have shown conclusively, uric acid is not toxic, and per se is apparently as innocuous as those other and intermediary products of metabolism which give rise to cystinuria and alkaptonuria.
The question then arises, Is gout haply due to a retention of other metabolites? That outbreaks of gout follow fast on the heels of dietetic irregularities is proverbially true. But there is no certain evidence that the symptoms generally ascribed to auto-toxæmia are referable to substances derived from the foodstuffs under the action of the digestive juices. Toxic as are peptones and primary proteoses when they gain direct access to the tissues, the symptoms produced in no way resemble those affiliated to alimentary toxæmia, much less those of gout. Rather, according to Adami, do they approximate to those typical of anaphylactic shock.
Normally, too, the mucous membrane proves an efficient barrier, these poisonous bodies during their passage through it being transmuted into harmless substances. Nor can we refer the symptoms of gout to a toxæmia secondary to intestinal stasis or other causes. In other words, it cannot be attributed to assumed toxic action on the part of the intermediary and terminal products of protein disintegration. For seemingly these chemical outcasts of the economy become progressively less toxic on their downward path to effete matter.
The diamines, too, produced by bacterial action on foodstuffs, are so minimal as to be negligible, while the toxicity of cholin and neurin is unestablished; and as for indol and skatol, they are with difficulty absorbed from the healthy colon. Experimental researches on carbohydrate and fatty disintegration have likewise proved sterile, while there is no evidence that the anaerobes present in the digestive tract produce ecto-toxins, or undergo lysis with release and absorption of their endo-toxins.
In short, it is but too clear from the foregoing brief résumé of recent experimental findings that, if uric acid cannot be held responsible for the causation of gout, there is no evidence likewise that the disorder owes its genesis to any other of the as yet isolated chemical products of gastro-intestinal digestive activities. Having dealt with this aspect of the question, we shall now pass on to consider whether the phenomena of gout can be more adequately explained on a basis of infection or sub-infection.
Infection or Sub-infection.—Our knowledge as to the exact manner in which local foci of infection work their malign effects almost daily undergoes expansion. It will be recalled that Stewart has shown that “bad teeth” are often etiologically responsible for tonsillar inflammation. It further is well established that streptococci are of common incidence in the tonsils, and Rosenow and Brown from experimental observation have established that these hemolysing organisms, migrating viâ the blood stream, exhibit a marked predilection for forming a fresh nidus in the gall bladder. Here they may initiate a cholecystitis, and secondly gallstones, and in sequence thereto the symptoms associated with gall-bladder-dyspepsia. The same formidable list of sequels may follow infection of the gall bladder from the teeth, stomach, or intestines, notably from the vermiform appendix.
In like fashion the origin of appendicitis may be traced back to septic foci in the mouth, tonsils, naso-pharynx, or to the gastro-intestinal tract. Here again there ensue the symptoms of so-called appendix-dyspepsia. As in the case of the gall-bladder variety, the primary lesion in the appendix may be latent, and the exact diagnosis may be a matter of great difficulty, often indeed only to be achieved retrospectively, viz., when abatement of the symptoms follows ablation of the appendix.
We see, therefore, how far-reaching are the consequences of local foci of infection in the mouth or elsewhere. Now, the gouty subject enjoys no immunity from the remote sequels of local sepsis. But as a rule, unfortunately, whatever be the nature of his dyspeptic symptoms, they are, like his dental anomalies, his tonsillar inflammations, forthwith dismissed as symptomatic of gout, not etiologically related thereto.
Now, I have seen pyorrhœa and chronic appendix-dyspepsia running side by side in the same subject with recurring classical attacks of gout in the big toe. The faulty teeth were extracted, and later the chronically inflamed appendix removed; and though he had an attack of gout shortly after the operation, there has as yet been no recurrence thereof.
Again, by the older writers “gout in the liver” was most firmly believed in—as one authority puts it, “a subacute catarrh of the intrahepatic biliary system which may lead to a subacute parenchymatous hepatitis”! But more pertinent to my point is the insistence of older authors upon the frequent association of gout and gall-stones. Senac, of Vichy, claimed indeed that out of 166 cases of biliary lithiasis 95 had gout or an hereditary predisposition thereto. Judging by modern experience, this is probably a gross over-estimate. In contrast, our own countryman Murchison dwelt upon the frequency of jaundice in gout independently of biliary colic. And, as we shall see later, Brinton held that many of the dramatic phenomena accredited to “retrocedent gout” were unrecognised examples of biliary colic.
But, controversy aside, the point I would lay stress on is, that we should refrain from labelling offhand “dyspeptic” symptoms in a “gouty” subject as gouty, this when we are so constantly confronted with local foci of infection in the mouth, or elsewhere, which afford us an explanation of the gastro-intestinal symptoms at once more obvious and more rational. This also the more especially in that—as far as subjective symptoms go—those deemed typical of so-called “gouty” dyspepsia are indistinguishable from those met with in appendix- or gall-bladder-dyspepsia. Indeed, I might go further and point out that the variations in free HCL in the gastric juice—as observed in gout—conform to those met with in the above disorders. Thus, in “gouty” dyspepsia, the free HCL may be normal, in excess, or wholly absent, as in gall-bladder or appendix-dyspepsia. I would therefore plead that in any “dyspepsia” arising in a genuinely gouty subject we endeavour to elucidate the exact nature of the underlying lesion, but to this we shall return again when discussing diagnosis.
Again, the fact that gall-bladder or appendix lesions may be the outcome of septic foci in the mouth enables us the more easily to explain the not infrequent co-existence of gout and glycosuria. For an infected gall-bladder may by extension determine a chronic pancreatitis.
Lastly, what of the relationship of local foci of infection to “gouty” synovitis and arthritis? Is one focal infection more than another particularly related to arthritides? Whatever be the true inference, if we take arthritides as a whole, nothing seems so efficient a cause of their production as oral sepsis. Accordingly, some are inclined to think that organisms, e.g., streptococcus viridans, at the roots of the teeth or others in the tonsillar crypts, pass, viâ the blood-stream, direct to the joints. Others, again, hold that, given oral sepsis, infection of the stomach and lower levels of the alimentary tract and its accessory cavities ensues. And in sequence thereto infection of the joints may take place from local foci throughout gastro-intestinal tracts.
Those who favour the view that direct infection viâ the blood from foci of oral sepsis is the more probable modus operandi are wont to produce the following points in support of their view. Arthritis, they say, is relatively rare in enteric fever. In yet another disorder, dysentery, which gives every chance of absorption from the intestine, arthritis when it occurs is seldom very acute, while in appendicitis it is distinctly uncommon.
On the other hand, we must recall that even in normal animals the alimentary and respiratory tracts, and alike the liver and kidneys, constantly afford cultures of pathogenic and non-pathogenic bacteria. Such was established by Adami and his co-workers, who moreover found that such organisms, through the agency of leucocytes, continually pass into the system, where subsequently in the healthy animal they as constantly undergo destruction.
If, however, inflammatory processes are at work, their migration into the tissues is favoured. For under such conditions leucocytes aggregate at the reactive focus, and concurrently, their migration being more active, larger numbers of bacteria achieve entry into the system. The subsequent course of events is determined by the number and virulence of the organisms that effect a lodgment in the tissues, where under favourable conditions they originate other foci of infection or sub-infection.
By sub-infection is understood the fact that microbes carried into the system undergo slight, if any, numerical increase, and do not set up foci of suppuration. Here we may note that “gouty” inflammation, however intense, never ends in pus formation. But, to resume, the bacteria, instead of multiplying, undergo lysis, and, their endo-toxins being released, the more highly specialised tissue cells in the vicinity are destroyed. Coincidently the lower grade connective tissue elements are by the self-same poisons stimulated to proliferate, and an area of chronic interstitial fibrosis is formed.
Incidentally this is interesting, inasmuch as the visceral organs in gout evince a tendency to fibrosis. But, as Gideon Wells observes, “the actual increase of uric acid in the blood and tissues in gout is so slight that we are not warranted in saying that the usual tendency to sclerosis in all the organs in gout is due to the action of uric acid rather than to some other unknown agent or agents.” In view of these revelations, is it not infinitely more likely that the chronic interstitial fibroses in gout are the outcome of such sub-infection?
The assumption gathers weight in light of the experimental proof adduced by Adami that not only tubercle bacilli, but streptococci and other organisms, taken orally, can gain an entrance into the system. Upon this basis we get a clear conception of the possible relationship of gout to local foci of infection. Thus, whether it be a condition of oral sepsis—pyorrhœa alveolaris, tonsillar sepsis, sinus disease, intestinal disorders, constipation, and so forth—we see that it is highly probable that organisms at any one of such infective foci may gain access to the blood-stream with subsequent installation of local lesions in joints or other structures.
Now, as pointed out, inflammatory states or functional derangements of the alimentary tract, whether focal or diffuse, favour the ingress into the tissues of organisms. Is it not reasonable, therefore, we ask, to suppose that the functional derangements which so commonly precede or accompany gout may modify the character of the intestinal flora, and promote their migration inwards in greater numbers? The inevitable swiftness with which relapses or exacerbations of this disorder follow even venial dietetic indiscretions distinctly favours this assumption, one, moreover, substantiated by the amelioration or immunity which follows abstention from the offending foodstuffs. The often prolonged course, too, of gout, and its marked liability to periodic recurrence, would be explicable as the outcome of a continued or intermittent series of sub-infections.
My conclusions then are that:—
(1) The majority of cases of gout are marked by the presence of local foci of infection, pyorrhœa alveolaris, tonsillar, pharyngeal or nasal sepsis, etc., or by gastro-intestinal derangements, constipation, etc.
(2) The said local foci should be regarded not as symptomatic of, but etiologically related to, gouty arthritis, and that the same is strongly indicated by the fact that
(3) Acute glandular affections of undeniably infective source—tonsillitis, pharyngitis, etc.—frequently and immediately precede acute paroxysms of articular gout, and, lastly,
(4) The gastro-intestinal defects, secretory or motor, which chequer the course of gout, enhance the pathological activities of the intestinal flora, and incidentally the liability to infection, at various sites of the alimentary tract.