Chapter XIV: Gout as an Infection

“The old order changeth, giving place to new,” and the uric acid theory having failed us, it is essential that we cast round for some other solution of the problem, carrying with us, however, this guiding principle, that _uric acid_, having lost its _etiological_ status, be viewed in its right perspective as not the cause, but the _consequence_, of gout.

Happily, with the advent of bacteriology our views, or rather our hazards, as to the nature of joint diseases underwent profound modification. But, strange to say, though quick to apprehend the significance of infection, its causal relation to other joint disorders, we still seem unaccountably loth to discard our time-worn conception of “gouty” arthritis as of purely _metabolic_ origin. This, to my mind, is the more remarkable in that the onset, clinical phenomena, and course of acute gout, and no less the life history of the disorder as a whole, are emphatically indicative of the intrusion of an _infective_ element in its genesis.

In developing this hypothesis I purpose devoting the present chapter to consideration of the frequency with which local foci of infection are met with in gout, the frequency, too, with which exacerbations of the disorder are presaged by acute glandular affections of undeniably infective source. The latter part of the text will concern itself with the rival claims of _auto-toxæmia_ and _infection_ or _sub-infection_. In the subsequent chapter we shall analyse critically the component elements of the acute paroxysm of gout, their compatibility or not with an infective origin. The affinities between gouty arthritis and the specific infective arthritides will then be noted, and, finally, an endeavour made to link up the specific stigmata of gout—its uratic deposits—with the postulated infective element.

LOCAL FOCI OF INFECTION

The extreme frequency with which _infective foci_ are met with in the victims of gout is by no means adequately realised. Moreover, we are only now beginning to appreciate the grave significance of such “nests” of infection and how devious are the ways in which they work their malign influence. For our forefathers gout began, and, forsooth, often ended, in the “stomach,” or it was the “liver” that was impeached. But the portal to the alimentary canal was for them only a cavity, the contained structures of which, albeit, to their mind often betrayed evidences of a “gouty diathesis.” They distinguished “gouty” teeth, “gouty” tonsillitis, “gouty” pharyngitis, even “gouty” parotitis; but all these they classed as tokens or sequelæ of gout—not possible causes or excitants thereof.

Nevertheless, their observations on “gouty” teeth are of deep interest, though their significance was misinterpreted.

Thus, Duckworth, for example, wrote: “The tendency to shed sound teeth has been noted with some frequency in middle or later life in goutily disposed persons, and they are more than others liable to occasional and fugitive attacks of pain in several sound teeth at a time, with a sensation as if these were starting from their sockets, being tender to bite upon.” In truth, a succinct picture of _pyorrhœa alveolaris_, of unprejudiced source, hence the more valuable.

Garrod again tells us that he saw an initial attack of gout supervene after extraction of a tooth, a sequence attributed by him to loss of blood. How interesting this, in light of the fact that exacerbations of joint disease have frequently been seen to follow the removal of septic teeth. The same authority also noted the incidence of a primary attack of gout following _epistaxis_, and the same after copious _hæmatemesis_, and Todd several times observed such articular outbreaks after _venesection_.

Lastly, says Garrod, “cases illustrative of the effects of the suppression of an habitual hæmorrhoidal discharge are by no means uncommon, and ... numerous instances arising from _boils and carbuncles_ have come under my notice.” By Garrod and his contemporaries all these various determinants of gouty paroxysms, _i.e._, loss of blood, etc., were believed to exert their influence _viâ_ the _nervous_ system, with consequent disturbed equilibrium of nutritive processes throughout the body. But while it may be admitted that depression of the _vis resistantiæ_ plays a part, it does so, I believe, by favouring the occurrence of _infection_.

Let us turn now to modern findings, and we shall see that they do but confirm those of the older clinicians. Lambert in 125 cases of gout found the teeth unsound in 82 per cent. of males and 1 per cent. of females, while in 9 per cent. of the former and 17 per cent. of the latter there was associated _chronic dyspepsia_. Two years after (1909) Wynn, Wirgman and Turner noted the invariable correlation of gout with local foci of infection. In the majority, _pyorrhœa alveolaris_ was present. _Tonsillar sepsis_, too, was not uncommon, and much more rarely _nasal_ disorders. Again, out of fifty-two examples of so-called “gouty” throat Edward McCracken found _pyorrhœa alveolaris_ to be present in thirty-nine, and Fenner also tells us that this affection is common in the subjects of gout.

In truth, the victims of _gouty_ arthritis are no more immune from _dental_ lesions than those of other types of joint disease. Thus, Mr. Macdonald, dental surgeon to the Royal Mineral Water Hospital, Bath, informs me that this form of _oral sepsis_ is extremely common in _gouty_ individuals, and in my experience it is but rarely that evidences of its presence are not forthcoming in these subjects. The desirability of early recognition of such foci—in light of their highly probable _etiological_ significance—can scarcely be overestimated. For their consequences, both local and remote, are of paramount importance.

Thus, G. I. Stewart’s recent observations have conclusively demonstrated that “bad teeth” are causally related to _tonsillar_ affections. How illumining this, in view of McCracken’s experiences in “gouty throats.” As we saw, _pyorrhœa alveolaris_ was present in more than half the examples. But, more pertinently to the point at issue, he comments on the frequency with which the victims of gout develop _acute tonsillitis_, of lacunar or parenchymatous type, also that such attacks frequently precede outbreaks of _arthritic_ gout. Duckworth again noted the same liability of the gouty to unsound teeth and tonsillitis, and that the latter was often followed by articular outbreaks. Luff also observed that “gouty” tonsillitis was occasionally a precursor of articular gout, always subsiding on the appearance of the latter complication.

Again, acute and chronic _pharyngitis_ are proverbially common in “gouty” subjects. Moreover, in both types the subsidence of the throat affection has frequently been signalised by an articular outbreak of classic site. _Parotitis_, too, has been repeatedly met with in gout, and, according to Luff, “rapidly subsides on the appearance of regular gout in one or more joints.”

In truth, whether we peruse recent or older works on gout, we cannot fail to remark the unanimity of opinion as to the frequency of incidence of these _glandular_ affections—these states of _oral sepsis_—in the subjects of _gout_. Equally noteworthy is their insistence on the constancy with which such local affections have proved harbingers of oncoming _articular_ outbreaks. Lastly, the mere fact that our forefathers dignified these local disorders with special appellations, “gouty” tonsillitis, pharyngitis, etc., is cogent proof that they regarded them as among the integral features of gout.

Now, as to the true significance of these acute _glandular_ affections, held by clinicians of repute to be of “gouty” origin. What of “gouty” tonsillitis, pharyngitis, etc.? Still more, what of our deductions regarding the relationship of these same when met with in association with other joint disorders? Do we not hold them each and all as evidences of _infection_—“acute rheumatism,” “gonorrhœal arthritis,” etc.?—and we may well ask, Why not in _gout_?

Says Duckworth, “Angina tonsillaris—very painful but not suppurating—may in the gouty suddenly yield to an acute articular attack.” Is it not here more than likely that the tonsil was the initial site or portal of _infection_, and the arthritis _secondary_ thereto? Is not this same interpretation in all probability true also of all forms of “gouty” throats when followed by _arthritic_ outbreaks?

The marvel, then, is that not only have we held, but apparently many still hold, that the tonsillitis, pharyngitis, even the gingivitis—like the subsequent articular lesions—are one and all attributable to the underlying _gout_. We certainly would not do so in the case of any arthritis other than “gouty,” and to my mind the time is ripe for a change of attitude. The “gouty” throats, like the “gouty” teeth, should be regarded not as symptomatic of gout, but _etiologically_ related thereto. We should cease to talk of “gouty” throats, teeth, etc., should renounce the prefix, for there is nothing _specific_ of _gout_ either in the tonsillar, pharyngeal, or dental lesions. We should instead view these various local disorders in their true perspective as _foci of infection_, _causally_ related to the subsequent and _secondary_ “gouty” arthritis.

_Gastro-Intestinal Disorders._—It is a matter of common experience that acute attacks of gout are often preceded by or associated with flatulence, heartburn, acidity, loss of appetite, confined bowels, scanty, high-coloured urine, and a feeling of lassitude. In short, nothing is more certain than that exacerbations or relapses very commonly follow symptoms referable to gastro-intestinal and hepatic disorders.

How well established is it that these subjects after unusual, though not necessarily excessive, indulgence at the table, almost inevitably, and sometimes almost immediately, suffer twinges in the big toe, if not frank outbreaks of gout. Such reaction seems to indicate clearly that the functional disturbances in the alimentary tract stand in some causal relation to the subsequent arthritic phenomena. The assumption gains colour, too, from the very certainty with which freedom from such gouty manifestations is attained by abstinence from, or more moderate indulgence in, articles of diet predisposing to such ebullitions.

So much by way of prelude as to the probability—attested by clinical observation and the results of treatment—that the _intestinal canal_ is often the source of the responsible microbe or toxin. Let us now pass to consider what factors other than an _oral sepsis_ may favour the incidence of _functional_ disorders of the _alimentary_ tract.

_Variations in Free HCL._—Some years ago Grübe and Falkenstein found that in gout the hydrochloric acid of the gastric juice, far from being increased, was in most cases _diminished or wholly wanting_.

Now, as we know, the gastric juice when of normal acidity is quite capable of dealing with moderate quantities of pathogenic bacteria. But in the presence of _oral sepsis_ it is probable that a greater number are swallowed than can be satisfactorily coped with.

Given therefore excess of pathogenic organisms and _relative insufficiency of free HCL_, conditions favourable to the growth of bacteria ensue, while incidentally the chance of such reaching the intestine is materially enhanced.

When, however, the defensive barrier is wholly withdrawn, viz. when there is an absence of free HCL, then of course the necessary inhibition of microbic growth fails of achievement. Moreover, also owing to diminished acidity, ill-digested protein substances gain access to the intestine, and their subsequent putrefaction is favoured.

In opposition to the foregoing, many hold that an _excess of free HCL_ in gout is not uncommon, and unquestionably some are thus troubled. The pernicious effects of the hyperchlorhydria are accentuated by the fact that intestinal indigestion ensues secondarily, owing to the acid chyme completely antagonising pancreatic secretion and thus impairing digestive capacity.

_Intestinal_ rather than gastric indigestion is, I think, more typical of the gouty subject. It will be recalled that the food nucleins are unaffected by the gastric juice, and though the protein moiety is split off from the nucleinic acid by the pancreatic ferments, yet neither the poly- nor the mono-nucleotides are thereby acted upon. It is in truth the _succus entericus_ with its nucleotidase that plays the most important digestive _rôle_ as regards nucleins, breaking them up into nucleosides which are, to a large extent, absorbed as such.

To resume, this condition of _intestinal indigestion_ may arise from a variety of causes: excess or deficiency of gastric juice, defective motility, and diminished secretion of intestinal juices, and in all cases improper food may determine such _intestinal derangement_.

The clinical features presented are very variable. It is often difficult, if not impossible, on the basis purely of the subjective symptoms, to decide in any given instance how far the symptoms are referable to _intestinal stasis_, or to a _chronic infection_, with a resultant catarrhal state of the mucosa, or to both causes combined in varying proportions.

But, be the explanation what it may, in our experience the most common antecedent or concomitant of gout is _intestinal dyspepsia_. Its secondary consequences are far reaching, especially if the small bowel be involved, catarrh of which may lead to _reduction_ in the secretion of _bile_ and _pancreatic juice_.

How commonly in these cases do we meet with symptoms indicative of sluggishness of the hepatic functions, such as turbidity of the urine, a pale or abnormally dark colour of the alvine evacuations. Also, whatever be its true etiology, they exhibit not so uncommonly _sugar_ in the urine, the so-called “gouty” _glycosuria_.

Now, as a mere glance will show, diminution and impairment of the biliary and pancreatic secretions have far-reaching consequences. Foodstuffs undergo abnormal changes, are less easily absorbed, and simultaneously chemical products are formed which irritate the intestinal mucosa. Nor do the baneful effects cease here, for, owing to the unusual nature and reaction of the intestinal content, the _bacterial flora_ in the bowel undergo modifications.

Thus, organisms normally present only in small numbers in the small intestine find the altered medium more suitable for their growth and multiplication; while others, whose usual habitat is the large bowel, migrate upwards, and infect the ileum and duodenum, and ultimately the biliary and pancreatic passages.

In the presence of such deficiency in the intestinal juices, proteins are imperfectly digested, and putrefaction under microbic action favoured. At the same time the digestion of carbohydrates is impaired, organic acids are formed, and gases in larger amounts liberated. Ultimately, owing to absorption of these irritating products, a condition of _chronic toxæmia_ results.

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.