CHAPTER XX

SPRUE

DEFINITION AND SYNONYMS

=Definition.=—Under the designation sprue we have a form of chronic diarrhoea characterized by periods of improvement alternating with a return to the previous condition. The disease is afebrile, of insidious onset and first manifests itself by soreness of the buccal mucosa and vague digestive disturbances.

The soreness of mouth and gullet is soon followed by erosions, especially at the site of the posterior molars, and a bare raw tongue. Exceedingly characteristic are the voluminous, frothy stools which are evacuated chiefly in the morning hours. The patient becomes weak, emaciated, irritable and of an earthy pallor.

The disease chiefly affects Europeans who have lived in Southern China, Cochin China and Java, and unless treated early tends to progress to a fatal termination.

=Synonyms.=—The word sprue is a corruption of the Dutch term “spruw” used to designate this tropical aphtha or aphthous stomatitis. The name psilosis, meaning bare, was suggested by Thin and is the term employed in many books instead of the better recognized designation, sprue.

Other designations are: Chronic diarrhoea of the tropics, Ceylon sore mouth and Cochin China diarrhoea.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—The French (1868-1872) described this disease under the name of chronic or endemic diarrhoea of Cochin China and noted its resemblance to Moore’s “Hill Diarrhoea.” In 1876 Normand incorrectly associated _Strongyloides_ with the disease.

The physicians of the Dutch East Indies described the disease under the designation “spruw” and Manson in a very complete description of the disease called it “sprue,” a corruption of the Dutch name.

It is interesting to note that Hillary in 1766, described a similar disease of Barbadoes, W. I., which he called aphthoides chronica.

=Geographical Distribution.=—It is particularly prevalent in South China and the East Indies. India and Ceylon are also regions of the disease. In the West Indies it has been carefully studied, in Porto Rico by Ashford, and of particular interest is the fact that Wood has recently insisted on the presence of sprue in the Southern States of the U. S. The Philippines and tropical Africa are also sections from which the disease is reported.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The cause is unknown. The disease makes its appearance chiefly in Europeans who have lived many years in the tropics and may not show itself until the patient has returned home. (In one case reported by Thin seventeen years after the return home.)

It seems to select those who are weakened by dysentery or other debilitating diseases, or who are compelled to subsist on indigestible food or to lead a life of exposure to hardships. Women in whom the menstrual flow is excessive or who are in the period of lactation seem to be especially susceptible. Some think alcoholics more susceptible. The idea has been advanced that the abuse of calomel has been a factor and this view is one to be given weight because it is well recognized that at the present there is much less sprue than formerly and with this there has been a more rational use of calomel. The excessive use of highly seasoned food, so common with Europeans in the tropics, may have an influence.

Some have thought that sprue was the manifestation of a tropical pancreas; at first congestion and later exhaustion of its function. The character of the stools lends support to this view.

At one time it was thought that _Strongyloides stercoralis_ was the cause; this idea had its origin in the finding of these larvae in the stools of a patient with Cochin China diarrhoea.

Certain authors have considered bacteria giving a granulose staining reaction as the cause while others have thought cocci to be concerned.

Kohlbrugge found organisms resembling _Oidium albicans_ in the intestines, oesophagus and tongue. He found similar organisms in the stools and tongue scrapings of cases of sprue. Beneke found bacilli in the tongue, oesophagus and intestines and considered these as causative, regarding the thrush-like membranous deposit as connected with the cachectic state and not causative.

Bahr is inclined to believe that _Monilia albicans_ (_Oidium albicans_) is the cause, as he found these saccharomycetes in the deep layers of the tongue, in the mucoid coating of the intestines and in the deposit in the oesophagus. He thinks it the ordinary thrush species which may take on greater virulence in the tropics. Ashford states that he has found a species of _Monilia_, different from that of thrush, almost constantly in tongue scrapings and stools of sprue cases and he regards this species as the cause of sprue. He states that this organism is common in Porto Rico bread and thinks it possible that the disease is transmitted in this way. It has been called _Parasaccharomyces ashfordi_. It is a round yeast, 4 to 7 microns in diameter. Wood has recently expressed the view that sprue is not infrequently mistaken for pellagra in the Southern United States.

Castellani, in a study of moulds of the genus _Monilia_ in sprue stools, holds them responsible for the excessive gas production, although not the cause of the disease. Various protozoa, as amoebae and spirochaetes, have been considered as possible causes.

While there does not seem to be any vitamine deficiency implicated yet there is disordered assimilation, which may be due to alimentary tract infection or to insufficiency of pancreatic functioning. It has been suggested that secretin deficiency is the essential disturbance.

=Epidemiology.=—The disease is rare in natives and is entirely endemic. Some authorities have suggested a greater frequency of the disease in those intimately exposed to a case, as in husband and wife or the members of a family.

Sprue is usually a disease of mature life and affects women more frequently than men. While climate cannot be considered as causing sprue yet the effects of hot climates in producing exhaustion states in Europeans must be borne in mind. The sprue patient should always leave a tropical climate.

PATHOLOGY AND MORBID ANATOMY

The changes in the alimentary tract apparently originate in the structures lying beneath the epithelial coverings, thus indicating that the toxic material acts through the blood rather than as a surface irritant to the mucosa. At first there is congestion of the underlying connective tissue with a round cell infiltration. Later on the epithelial covering of the alimentary tract suffers and auto-intoxication, as evidenced by indicanuria, becomes operative.

At autopsy the subcutaneous fat is found to have almost disappeared. The intestines, especially the ileum, show marked thinning, this atrophy especially affecting the mucosa, the surface of which is covered by a layer of dirty gray mucus. The submucosa generally shows connective-tissue increase. The gut is pale and diaphanous. The solitary follicles may show as small cysts filled with a gelatinous material or as ulcers.

The liver is markedly atrophied. The mesenteric glands are usually enlarged. The pancreas may show cirrhotic changes.

SYMPTOMATOLOGY

=A Typical Case.=—It is very difficult to obtain definite information as to the onset which is characteristically insidious.

There is usually first noted a sensitiveness of the buccal mucosa so that alcoholic drinks and acid or highly seasoned food cannot be taken without marked discomfort. A sense of fulness or distention in the epigastric region is often an early symptom. Frequently there is a history of a rather intractable morning diarrhoea which may alternate with periods of constipation.

The diarrhoeal movements are remarkably copious and soon change from bile-colored, liquid evacuations to the characteristic putty-colored, pultaceous, gas bubble permeated, offensive stool of sprue. While the patient experiences a sense of relief from the evacuation of the fermenting mass yet there is at times an excoriation about the anus which may cause pain when at stool. Neuralgic pains of the region of the anus may be present late in the disease.

When examined microscopically the stools are found to show much fat, yeasts and undigested food. The fats are chiefly in the form of neutral fats and fatty acids rather than as soaps. The reaction is acid. Nausea and vomiting, especially about noon, may be complained of.

While the characteristic stools best show the full development of the disease there are also changes noted in tongue and buccal mucosa. Following the marked sensitiveness of the mouth above noted there soon appears a redness of the sides and tip of the tongue with a glistening coating of the surface. Small vesicles later becoming superficial erosions develop along the tongue borders, frenum and buccal mucosa.

There is also congestion and swelling of the fungiform papillae.

Very characteristic are ulcers at the site of the rear molars (Crombie’s ulcers). Later on the tongue becomes bare, fissured and even glazed, as if varnished.

The gullet may be raw and very sensitive. The appetite is apt to be capricious and the patient may be very intractable, insisting upon dietary indiscretions which he knows will aggravate his condition. There is a progressive loss of strength, weight and energy. The liver progressively diminishes in size but is difficult to map out owing to the bulging, dough-like abdominal contents. The urine is usually free of albumen but shows marked indicanuria. Sprue is characteristically afebrile.

Anaemia becomes marked, the red cells going as low at times as under 2,000,000, per cmm. and the Hb. percentage less markedly reduced (color index above 1). The polymorphonuclears are reduced in percentage.

There is a tendency to depression and irritability.

The period during which sprue runs its course is very variable. Some cases drag on for ten or twelve years while others may be subacute in type, death ensuing within a year or two.

In addition to the typical or complete sprue described above Bahr would add: (1) _Incomplete sprue_, in which with typical stools there is no abnormal appearance of the tongue, and (2) _Tongue sprue_, in which with characteristic mouth involvement there is absence of the sprue stool.

Symptoms in Detail

_The Stomatitis._—At first we have a disagreeable bitter taste in an unusually sensitive mouth. Later there develop superficial ulcers along the sides and frenum of the tongue, which subsequently involve the buccal mucosa. The gums may be quite tender and saliva dribble from the mouth.

In the later stages the tongue becomes bare, red, fissured and glazed.

_The Stools._—Commencing as early morning diarrhoea, with at times alternating constipation, there gradually sets in that which makes for a diagnosis of sprue—putty-colored, fermenting, offensive stools which are extraordinarily copious.

They are also very fatty and of acid reaction. They show a proteid loss as well as lack of fat absorption.

_The Blood Findings._—There is a marked secondary anaemia with great reduction in red cells and Hb. percentage.

The color index averages higher than normal and with the poikilocytosis resembles the blood picture of an atypical pernicious anaemia. Nucleated reds are rarely found. The eosinophiles are reduced in percentage. The polymorphonuclears often show a great number of nodes, as 7 or 8 instead of the ordinary three.

There is a mononuclear increase with polymorphonuclear reduction. The white count is somewhat below normal—4000 to 6000.

_Other Features of the Disease._—The liver is notably diminished in size. The urine shows indicanuria. The patient has a dry earthy skin and may show oedema about ankles.

Mentally there is lack of concentration with marked irritability and moroseness. Tetany has been reported as occurring rarely in very severe cases. The abdomen is doughy and the temperature in the later stages tends to become subnormal.

DIAGNOSIS

_Thrush_ is characterized by the membranous coating which microscopically shows the fungus. It also is chiefly a disease of children and those who live under wretched hygienic conditions and with insufficient food. The characteristic stools are absent.

_Pellagra._—The stomatitis, diarrhoea and mental irritability are very similar in the two diseases. There is, however, absence of the sprue stools in pellagra and the periodical recurrence and skin manifestations of pellagra are absent in sprue.

Wood thinks that in the absence of any evidences of organic nervous disease in sprue we have an important differentiation as he finds that pellagra has as great a tendency to invade the nervous system as has syphilis. Salivation is marked in pellagra, not in sprue. The two diseases, however, are best differentiated by the darker, more fluid, less copious stool of pellagra as contrasted with the copious, light colored stool of sprue. Stools containing great amounts of undigested fat are most characteristic of sprue; fat absorption in pellagra is about normal (95%) while in sprue it is only about 75%.

_Syphilis_ with its buccal mucous patches or geographical tongue may be mistaken for tongue sprue.

=Hill Diarrhoea.=—Many authorities do not consider this as a disease distinct from sprue. The English, however, note the features of its occurrence only at high altitudes; thus persons going to Simla suffer from hill diarrhoea but upon their return to the sea level the disease disappears. The characteristic features of hill diarrhoea or Simla trot, as it is often called, are the passage of from 2 to 6 watery, whitish stools in the early morning hours. The patient is usually free from diarrhoea in the afternoon. The color may resemble that of freshly made whitewash, hence diarrhoea alba.

At first it is only the annoyance that is complained of but later on the appetite is lost and the patient becomes weak.

There is an absence of the sprue mouth. The laboratory diagnosis, other than the finding of excess of fatty acids, soaps, undigested food remnants and yeasts is unimportant.

PROGNOSIS

While the disease responds to treatment in those who are not too far advanced yet it always should be considered a serious affection. The chances of a complete restoration to health are better for those who can leave the tropics and reside permanently elsewhere.

TREATMENT

It is essential that the patient possess the will power to carry out the course of treatment; the clothing should be of wool to prevent chilling and the patient should remain in bed until his condition has decidedly improved.

_The Milk Treatment._—A preliminary dose of castor oil is given and when this acts the patient should begin taking milk as the sole food. At first about 4 pints of skimmed milk are given daily. The milk should be given in two-hour feedings, well warmed and taken through a glass tube or with a teaspoon—it should not be drunk. As the stools become less frothy the amount of milk is increased so that the patient takes from 6 to 7 pints daily. Milk should be the sole food for six weeks from the time the stools become solid and the mouth symptoms disappear. Rele prefers buttermilk to skimmed milk. Eggs are usually well borne after the milk course. Stale bread or toast is cautiously added and then some fish or chicken.

At times the patient seems benefited by giving a meat treatment day once or twice a week during the course of the milk treatment.

_Meat Treatment._—If the patient is very ill it may be advisable, after the preliminary dose of castor oil, to give meat juice obtained by expressing the juice from slightly broiled meat, about 2 teaspoonfuls every half hour. If possible however one starts in with the meat cure, which is about 4 ounces of a lightly broiled chopped-up beefsteak, every four hours. Raw meat is usually given in this treatment but there is danger of _T. saginata_ infection.

At least 4 pints of warm water should be taken daily but not at the same time the patient eats the meat. Rest in bed and the avoidance of chilling are important measures. In all food treatments we should avoid forcing the patient to eat—it is better to give food only when the patient desires it.

Some prefer to alternate the milk treatment with the meat one.

_Fruit Treatment._—The patient is allowed fruit in great abundance. Strawberries, peaches, grapes, ripe gooseberries and fully ripe bananas are usually recommended. Papayas are

## particularly well suited. Pomegranates are also highly recommended.

Sour or fibrous fruits should be avoided. Strawberries and milk are highly advocated. Cooked strawberries or other cooked fruits do not benefit the patient, the curative principle being apparently destroyed by heating. At all times alcoholic drinks and highly spiced foods should be avoided.

The only drug that has been advocated to any extent is yellow santonin, in doses of 5 grains, night and morning. It is very doubtful if any drug treatment is of the least value.

LeDantec, with the elimination of the granulose bacteria in mind, has recommended the cutting off of carbohydrates and the giving of a strictly albuminous diet. Subsequently he gives lactic acid producers as contained in _Bacillus bulgaricus_ preparations.

Schmitter has recommended emetine in the treatment of sprue, but Ashford has found this drug, as well as santonin, of negative value. Brown has had success in treating a case of sprue with pancreatin, 30 grains daily. Since then he has had marked success in three other cases. He now combines the pancreatic extract with calcium carbonate.

In connection with Ashford’s work with a specific _Monilia, M. psilosis_, cases of sprue have been treated with vaccines made from this organism.

An autolysate of the cultures is sterilized at 56°C. for an hour and then centrifugalized. A one per cent. suspension of the sediment is used for injection increasing from about 0.1 cc. to 1 cc. at weekly intervals. Five or six injections are given.

It is stated that the symptoms at the start of the treatment are aggravated.

SECTION IV

HELMINTHIC INFECTIONS

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