Infantile Gout

While subjects of gout have told me that they had had an attack in their teens, I have never myself seen an instance. Still less can I claim to have seen what I felt justified in calling “gout” in children. On the other hand, if, as one authority states, “tonsillitis (quinsy), enlarged tonsils, granular states of the pharynx, and catarrhal conditions of the throat and respiratory mucous membranes are not infrequent expressions of gouty inheritance in children,” then, of course, all of us must be quite familiar with “infantile gout.”

But even this formidable list of legacies from gouty parents is eclipsed by a more recent writer, J. Comby (1902), who, discussing “infantile arthritism,” divides children coming of gouty stock into two types: the “lymphatic” and “nervous.” The children of the former class suffer from fleeting swelling of the lymphatic glands, rhino-pharyngitis, tonsillitis, and, if they be girls, from chlorosis. Also they are given markedly to tachycardia, bradycardia, and vasomotor ataxia. They are also especially liable to asthma and the crises of dyspnœa, and pulmonary congestion may alternate with urticarial and eczematous eruptions. Truly, their lot is hard, for they fall a ready prey to colic, constipation, all varieties of dyspepsia, not to mention nocturnal and diurnal enuresis!

Comby also claims that these gouty children are especially liable to recurrent or cyclical vomiting. In this matter he is confirmed by J. Thomson, who noted that these children not infrequently give a history of having had asthma, urticaria, eczema, stammering, and other nervous complaints, also that in many instances uric acid crystals or a copious deposit of urates have been noted in their urine.

As to the “nervous” type, they labour with insomnia, night terrors, convulsions, and when older with migraine. To these liabilities must be added undue proneness to acne, seborrhœa, psoriasis, chilblains, angio-neurotic œdema, urticaria, etc., not to mention muscular and joint aches and pains.

Whether this medley of distempers can with any pretensions to scientific reason be affiliated to a gouty heritage, or whether they can be regarded as expressions of a budding “gouty diathesis,” is, I submit, of the nature of pure speculation. That the child who suffers with cyclical vomiting may show uric acid crystals or urates in his urine is certainly no proof that he has inherited gout, much less that he is actually “gouty.” In uro-lithiasis the uric acid is precipitated in the urinary passages, viz., strictly speaking, outside the body, whereas in gout the pathological error originates within the organism. More apposite is Uffenheimer’s observation, previously noted, that children of this type suffer the same disturbances of purin metabolism as are met with in adult gouty subjects.

If the fact is confirmed that the output of exogenous purin in such children is diminished or retarded, it would certainly be a most interesting finding, possibly with a now unguessed-at significance. But we should recall that even in the subjects of regular gout such is not invariable, and, moreover, occurs in diseases other than gout. Pending further exact investigations I think it would be wiser not to indulge in such vast generalisations, mindful of the sentiments expressed by the illustrious Sydenham in his letter to Dr. Gould:—

“I have bin very careful to write nothing but what was the product of careful observation. So when the scandall of my person shall be layd aside in my grave it will appear that I neither suffered myselfe to be deceived by indulging in idle speculations nor have deceived others by obtruding anything to them but downright matter of fact.”

CHAPTER XXV
OCULAR DISEASE IN THE GOUTY

By W. M. Beaumont

With the passing of Jonathan Hutchinson disappeared the premier British exponent of l’arthritisme, that generic term so attractive to our French confrères. Whether gout and rheumatism are branches of one common stem need not detain us, for it is an abstraction more suitable to the philosophic age of medicine before pathology emerged as an exact science. Be this as it may, there has been in the past, and there still remains in the present, as a bond of union, a universal belief that both are subtle causes of disease of the eye. But the age of hypothesis is giving place to the era of facts, and we find in recent writings a more cautious expression of individual opinion, a less dogmatic positivism regarding the relationship of gout and rheumatism to ocular disease.

In referring to modern text-books we find Parsons[44] describes gout as one of the “alleged causes” of iritis. In rheumatic iritis he states that the patients “are often gouty.” The gouty nature of iritis is indicated by the similarity of onset of some cases of iritis with that of gout. “Iritis in an elderly patient is likely to be gouty, often starting suddenly in the night and sometimes ushering in an attack of gouty arthritis.” In episcleritis “rheumatism and gout are commonly indicated as the chief causes.”

Werner[45] includes gout in a list of disorders of metabolism which produce iritis “by means of toxins of a chemical nature.”

Sim[46] considers that iritis occurs in gout “as the result of some toxic influence”; and in addition he says, “Iritis is to be met with in gout.”

These authors express accurately, I think, the present views with regard to gout as it affects the eye; with each there is a tone of restraint and suggestion rather than of boldness and assertion, and the contrast to Hutchinson’s emphasis is noteworthy: “I believe,” he tells us, “that iritis due to the arthritic diathesis is a common malady.”

Among the many and indiscriminate diseases of the eye which have been considered to be due to gout are included blepharitis, conjunctivitis, episcleritis, scleritis, orbital cellulitis, neuro-retinitis, retro-bulbar neuritis, optic neuritis, optic atrophy, iritis, cyclitis, choroiditis, glaucoma and retinal hæmorrhage. Truly an all-embracing rather than an eclectic list, a medley of diseases without any melody.

Evidence of Gout in the Eye.—When we inquire what is the evidence which justifies the belief that gout causes ocular disease we find little more than a traditional hypothesis inherited in a long line of succession from the Fathers of Medicine. Nevertheless the opinion that there is a connection is widespread, not only in Europe, but also in America.

In considering this relationship we cannot overlook the effects of the diathesis on other viscera. How in these is a diagnosis of gouty origin arrived at? It would appear that the assumption of an irregular form of gout is based upon the following observations:—

(i.) That it sometimes happens that an undoubted attack of articular gout aborts and is followed by symptoms referable to a grave visceral disorder, e.g., gout in the stomach (retrocedent gout);

(ii.) That sometimes the converse occurs, viz., that an attack of visceral disorder may suddenly be replaced by an acute articular manifestation;

(iii.) That such visceral derangements may alternate, not only with articular, but also with other, such as cutaneous, outbreaks;

(iv.) That eye disease has been known to wax and wane in unison with concurrent arthritic gouty manifestations;

(v.) That occasionally in gouty people an attack of iritis of sudden onset in the night has been followed by remission of the symptoms in the day[47];

(vi.) That visceral symptoms in the gouty are anomalous and inexplicable on any other basis;

(vii.) That the treatment usually advocated for gout has a favourable influence.

Deposition of Urates.—Two cases are recorded by Garrod in which there was a deposit of urates in the sclera. These instances do not appear to have been confirmed by other observers, and they may be regarded as exceptional cases, occurring, it should be noted, in the outer envelope of the eye. But though these tophaceous deposits may occur in the sclera and in the eyelid, they have never been known to invade the intrinsic structures, such as the iris or ocular media. The eye, in fact, is on all fours with the sites of urates elsewhere—deposition occurs in parts of relatively low vitality.

Although urates are not found within the eye, there is in other morbid ocular conditions quite frequently a deposition of foreign matter, such as alien crystals, of varied description. For instance:—

In the sclera on rare occasions we find osteomatous degeneration.

In the choroid there may be true bone which forms a cup so extensive that it can be felt by the finger, or, again, there may be calcareous plaques.

The retina may undergo colloidal changes or be the site of carbonate of lime or of cholesterin.

The vitreous may sparkle with showers of cholesterin.

The lens may contain both tyrosine and cholesterin.

The aqueous shows similar crystals.

In the iris degenerative calcareous or osseous deposits are occasionally seen.

The cornea may be affected by hyaline degeneration with deposition of lime salts.

The conjunctiva may be calcareous.

In all these cases the foreign particles, whether crystals or otherwise, are usually the retrogressive changes of senescence proclaiming that the forces which make for degeneration are more potent than those which make for regeneration.

But urates are not found in the eye, even though the patient is gouty. On the other hand, both in gouty joints and in other similarly affected parts of the body we find a deposition of urate of soda.

Gouty Diathesis.—From the days of Sydenham—himself a martyr to gout—diathesis has been a name to conjure with, and an all-sufficient diagnosis. In the podagrous patient any intercurrent disorder, any inexplicable ache or pain, was ascribed to gout, and patient and doctor were alike satisfied. “Tempora mutantur,” but still we are prone to call morbid conditions gouty when they occur in gouty people.

If we accept the theory that gout is due to an excess of uric acid in the blood, the view which I have expressed elsewhere[48] that gout does not cause iritis is directly challenged. For if it be granted that a sudden outpouring of so non-toxic an acid causes an acute inflammation—for instance, in the synovia of the great toe—why should not our faith incline us to go further and find in this malevolent, though bland, acid a source of inflammation affecting the fibro-muscular meshwork of the iris?

If, however, we adopt the infective theory, then the association of the uratic deposits no longer dominates our creed—we view them as mere clinkers and by-products erupted from the furnace.

The infective theory of gout also lends plausibility to an association with iritis, for this latter is a disease of infective origin. For the intimate relationship of all forms of asthenic arthritis with iritis is of very frequent occurrence, but is practically never seen in the more sthenic arthritides: rheumatic fever, acute gout and traumatic arthritis.

Nearly fifty years ago Jonathan Hutchinson drew up a “Report on the Forms of Eye Disease which occur in connection with Rheumatism and Gout.”[49]

At the present day it is not easy to differentiate his 117 cases according to modern classification, but he includes gout, rheumatism, rheumatic arthritis, etc. The differential diagnosis between gout and rheumatism was simplified by the creation of a mule—“rheumatic gout”—and upon its back were packed the doubtful cases.

Hutchinson’s views regarding the essential difference between gout and rheumatism are crystallised in his statement that in rheumatism there is an arthritic susceptibility to weather, in gout an arthritic susceptibility to diet.

Osteoarthritis also seems to have been included as one of the gouty diseases, probably because post-mortem examination revealed uratic deposits in the disorganised cartilage. This, however, would appear to be an epi-phenomenon, and must not be allowed to obscure the essential distinction between true gout and osteoarthritis. It is a sign of articular disorganisation of long standing, and is the homologue of the similar deposition of crystals, etc., already referred to as occurring in the eye as the result of chronic disease therein.

The significance of tophi, as the touch-marks of gout, is undoubted, but even if they are detected in the eyelids or elsewhere, we are skating on thin ice if we rashly declare that a coexisting intra-ocular disorder is gouty. Most forms of iritis betray the same clinical facies, although the etiological causes are diverse. But in none do we find any appearances pathognomonic of gout.

The argument that because a patient has tophi therefore the iritis is also gouty does not hold good, for gout does not confer immunity from other diseases, and even though we cannot prove an alibi for the diathesis, we can often in these cases also indict gonorrhœa, pyorrhœa or some other pathogenic agent.

The favourite site for tophi is one in which blood-vessels are sparse; but, although the cornea is void, imbibition of blood from the marginal looped plexus of capillaries and an abundant lymph supply provide amply for nutrition, and tophi are not found in this locality. The sclerotic, however, has a meagre supply of vessels, and for some unexplained reason tophi rarely invade it. In the eyelids, on the other hand, possibly from the cartilage being rich in sodium, tophi are occasionally seen. If we accept the tophus as the one unequivocal criterion of gout, we are not justified in labelling an iritis as gouty in its absence. If we do, our diagnosis is presumptuous and not absolute. Strictly speaking, the diagnosis cannot be made. We may the more readily admit our limitations, inasmuch as they are a blessing in disguise, and suggest a further etiological search.

In Hutchinson’s list of eye diseases which occur in association with rheumatism and gout there is a history of gonorrhœa in twenty-six cases, syphilis in seventeen, of both gonorrhœa and syphilis in six. Herpes occurred in two, pustular acne in one, eczema in one, albuminuria in one, ague in one. Bad teeth are reported in two. In all the total was fifty-seven cases out of 117 (48·7 per cent.) in which there was a possible source of infection. It is probable that this percentage would have been materially increased if at that time it had been recognised how great is the influence of pyorrhœa and other sources of infection in the etiology of irido-cyclitis.

With regard to all infections it is only in the present day that full advantage is taken of bio-chemical and bacteriological methods of differentiation. How frequently the true origin of disease must have been overlooked when the pallid spirochæte was unknown, when the Wassermann test was not applied, and when the complement fixation test for gonorrhœa was not recognised.

With regard to a combined cause it has been maintained that gonorrhœa is always more severe in the gouty than in other people, and it may be that the more intense the gonorrhœa the more likely may it be to produce constitutional symptoms, of which iritis is one. In all such the combination of gout and iritis would indelibly impress upon the mind of the surgeon the intimate association of joint and eye. It was long ago recognised that many forms of joint disorder were associated with iritis, and, as the cause of the arthritis was not always gout, Mackenzie introduced the generalisation “arthritic iritis.” “Not being able,” he tells us,[50] “to determine the diathesis which predisposes to this ophthalmia” (iritis), “I use arthritic as a conventional term, without adopting it in the strict sense of gouty.” The expression is well worthy of retention for the reason that it warns us to be prepared for an attack of iritis in many forms of arthritis and arthralgia.

In the following articular diseases the triad joint, muscle and nerve disorders is not uncommonly linked with iritis:—

In the following forms of arthritis iritis is less common:—

Iritis occurring in these last suggests the possibility of error in the diagnosis of the putative parent disease. Especially is the clinical similarity of gonorrhœal (polyarticular) rheumatism to rheumatoid arthritis to be borne in mind.

The Relative Incidence of Iritis.—In the text-books it is often stated that the syphilitic form of iritis is the one most frequently met with, and that gouty iritis, if it is met with at all, is much more rare. But in these comparative statements we have no clue to the frequency of iritis with syphilis, nor of iritis with gout. For a true analogy we do not want the syphilographer to tell us the aggregate number of cases of iritis that he has seen, but what is the percentage of cases of syphilis in which iritis occurs, and we want the gout physician to state his percentage of iritides in gout, or, negatively, what is the percentage of cases in which iritis does not occur.

If gout is a more prevalent disease than syphilis, it does not follow that “gouty” cases of iritis will be more numerous than those due to syphilis. Let us suppose, for the sake of clearness, that 1 per cent. of people suffering from gout get iritis, and that also 1 per cent. of people infected by syphilis get iritis, and that in a certain town there are two hundred people who are gouty and one hundred people who are syphilitic. It is probable that there will be two persons suffering from gouty iritis (always supposing there is such a disease), but only one from syphilitic iritis. The absolute totals will differ, but the relative will be identical. It is clear, then, that infectivity cannot be gauged by the statistical enumeration of the consulting-room. Gout is a rarer disease than our patients would have us believe, but accepting their views, even then we should expect to see more cases of iritis caused by it, if such existed; we should expect to find more definite proof of a causal connection, and less frequently a history of gonorrhœa, of pyorrhœa, and of syphilis.

No Uratosis, no Gout.—If we pin our faith to the equation

Hyperuricæmia + Uratosis = Gout,

we can at once exclude all cases of ocular disease as gouty in the absence of either factor. According to Garrod, “true gouty inflammation is always accompanied with a deposit of urate of soda in the inflamed part.” We should therefore expect that uratosis would occur in situ if an iritis were gouty. But it does not: the touch-mark is absent, and there are no chemical, pathological or clinical signs of urates in the iris after the inflammation has subsided. What then is the alternative? Either Garrod’s aphorism is inaccurate or iritis is never gouty. In other words, we must postulate that an iritis may be regarded as gouty without uratic deposits. If this be the case, the so-called gouty iritis may well rank with the occult migraines, flatulencies and acidities which are termed irregular, suppressed or latent gout. Strictly then it would be a latent gouty iritis fit to rank with that last refuge of the uric acid enthusiasts, the “latent nephritis” which they worship as the fons et origo mali of gout.

Metastasis.—The predilection of the gonococcus for synovial membranes is seen not only secondarily to urethral infections, but also in ophthalmia neonatorum, in which the joints of infants are affected sequentially to the eyes.[51]

The gonococcus also has been found in cases of peritonitis, pleurisy, pericarditis, etc., but it is said to have only once been isolated in the eye in iritis.[52]

It is not only the gonococcus which can initiate a metastasis from the eye to the joints, to the peritoneum, or elsewhere. The same process may be started by the bacillus typhosus, by the streptococcus of erysipelas, and by that of puerperal septicæmia.

De Grandmont[53] records the case of a young man recovering from typhoid, complicated with jaundice and nephritis, who was attacked by iritis with posterior synechiæ and hypopyon. Paracentesis was done, and the pus of the anterior chamber was transferred to agar-agar. Two days later a pure culture was obtained presenting all the reactions and characteristics of the bacillus of Eberth. Of this culture a small quantity was injected into the vitreous of a rabbit. A month later the rabbit was killed, when the liver and intestines were found to be infiltrated with the same bacillus of Eberth.

In erysipelas de Grandmont has seen a hyalitis from which a culture was grown on gelatine that presented all the morphological characteristics of erysipelas.

He has also met with a case of hyalitis associated with puerperal septicæmia, and he has no doubt that it was the result of a similar microbic invasion of the vitreous.

Gout does not render patients immune from tuberculous, syphilitic or gonococcal disease, and when in such so-called diathetic stocks an iritis occurs, especially in gonorrhœa, years after the primary disease, it is probable that gout, rather than lues, will be assigned as the cause.

The local appearances of iritis are identical in gonococcal and other infective iritides; they resemble clinically those seen in syphilis and tubercle except that in these there are sometimes condylomata of the iris in the one and tuberculous nodules in the other. To be comparable a gouty iritis should be characterised by iritic tophi.

“Arthritic” Iritis.—Forty-eight is a large percentage in Hutchinson’s cases of ocular disease associated with gout and rheumatism, and it is justifiable to assume that there was something more than coincidence in the triple entente of diathesis, arthritis and iritis. But the fact that the poisons of syphilis and gonorrhœa, etc., are potent causes of iritis is indisputable, and therefore the patients might have suffered from it even if they had never had either gout or “rheumatism.” Consequently these articular diseases are both superabundant and superfluous, and they may have no etiological status. A patient afflicted with arthritis is very susceptible to an associated attack of iritis provided that there is a septic focus anywhere in the body.

A practical point to remember, especially in gonorrhœa, is that the onset of joint trouble should warn us to anticipate the possibility of an associated iritis and should prompt us to instil atropine at an early stage. We should forestall the disease by treating the suspicion. The frequency with which gonorrhœa is followed sooner or later by iritis entitles this ocular phenomenon to be considered a secondary symptom of gonorrhœa, as it is of syphilis.

Before the potency of distant infective foci (for example, in nasal disorders, pyorrhœa, sinusitis, etc.) to produce ocular disease was recognised, there was justification for the inclusion of a so-called idiopathic iritis, but it is seldom now that we have to be satisfied with this negative diagnosis. Nevertheless the assignment of a toxæmic etiology must be based on a definitely ascertained focus of toxic absorption, or failing this, at least on symptoms of general malaise which render such a focus highly probable.

Frequency a Factor in Diagnosis.—It was known a century before the birth of bacteriology that gonorrhœa caused iritis. It was also noted that certain constitutional symptoms occurred in syphilis, and that among them not infrequently iritis was one. Observation and deduction was the process with our forefathers, and it seldom led them astray.

If in any sequence of events cause and effect are to be established when there is no obvious proof of connection, we may have to be content with an empirical diagnosis, and this was the position before the discoveries of bacteriology enabled us to place the etiology of iritis on a firm basis. How then did our ancestors know that syphilis and gonorrhœa caused iritis? Was it not—

(1) That the frequency of the association was the essence of the diagnosis,

(2) That there was absence of any other recognised cause, and

(3) In the former disease the effect of anti-syphilitic therapy?

Applying these rules to gout, we find—

(1) No marked frequency of association of ocular disease and gout,

(2) That when iritis does occur there is often some other possible source of origin, and

(3) That anti-gout treatment has only a doubtfully beneficial effect.

“Gouty” Iritis is not a Clinical Entity.—Before a symptom or affection can be classed as secondary to a primary disease there must be evidence of a connection stronger than post hoc, ergo propter hoc. For instance, in syphilis an iritis frequently follows which may be of the specific condylomatous type, and a laboratory examination of the inflamed iris may demonstrate the presence of the spirochæte. On the other hand, an iritis occurring in a gouty patient is indistinguishable from that form which results from infections of undifferentiated type. Moreover, iritis so seldom occurs associated with gout, and when it does there are so often present other well-recognised possible causes, such as pyorrhœa or gonorrhœa, that the doubt about the paternal relationship of gout to the iritis is overwhelmingly strong.

In the following table a comparison is made between types of iritis:—