GENERAL ARTICLES. 47

TREFOIL DERMATITIS

QR THE SENSITISATION OF UNPIGMENTED SKIN TO THE SUN'S RAYS BY THE INGESTION OF TREFOIL.

By SYDNEY DODD, D.V.Sc., F.R.C.V.S., Lecturer in Veterinary Pathology· and Bacteriology, The University of Sydney, New South Wales.

FOR a good many years a condition affecting the domestic herbivora has existed in certain parts of New South Wales under the name of <c aphis disease." Its known geographical distribution extends to roughly about 250 square miles, and it is highly probable that the area over which it occurs is much larger. The disease consists in a more or less severe inflammation of certain parts of the skin, accom­panied by exudation and irritation. Occasionally, necrosis of the tips of the: ears may be seen. Frequently the affected part becomes covered with crusts or scabs of dried exudate and blood, or, on .account of the animal biting or scratching the part, the skin may be removed and large superficial wounds appear.

The mortality is practically nil but the economic loss in various ways is considerable.

The disease is observed principally in the spring, viz., during the months of August, September, and October. Very frequently at this period large numbers of sheep are affected after shearing, mainly in the region of the back. The ears and noses of shecp are also the seat of lesions, chiefly during the spring, but apparently also at other times of the year. In the latter case it is mostly young sheep that are affected. The symptoms in sheep are that soon after being shorn the skin along the back becomes swollen. An exudate then appears upon this part, and it may dry up in the form of crusts or scabs. There is intense itching of the affected area, and the animal bites, rubs, or scratches it, with the result that considerable areas may be rendered quite raw. When the ears or noses are affected the parts are swollen, with an accompanying exudation of a clear, yellow, sticky fluid (plasma), which often forms thick crusts. These may be mixed with dried blood as the result of scratching or rubbing the affected parts. If the exudation on the ears is scanty, then a marked desquamation of the skin of that region is often seen. In young sheep dry necrosis of the tips of the ears is not uncommonly met with. Suppuration and ulceration of eroded areas may occur and at times be serious, but these must be viewed as complications.

In horses and cattle the condition is seen in those possessing white or pink skin, i.e., unpigmented skin, and it affects those areas only, pigmented skin remaining quite unaffected. In sheep, also, it is the unpigmented skin that is attacked.

The condition is called aphis disease by stock-owners because they firmly hold the opinion that it is caused by aphides, which are very prevalent in those localities in the springtime. It has been observed that the disease in sheep is mainly coincident with the shearing season. It also occurs when trefoil is green and abundant. This latter, however, they consider has no connection with the -disease except that the plant is a favourite haunt of aphides.

GENERAL ARTICLES.

The following are a few extracts from stock inspectors' reports. concerning this disease in various districts.!

Stock inspector at Coon amble reports in 1911 a dermatitis affect­ing sheep. Symptoms-lips, nose, ears affected. There appears to be considerable irritation of the skin, as the affected sheep scratch their heads with both hind feet, causing raw surfaces. They also gnaw and bite at their loins. The skin is moist and sweaty. The ears of the lambs are scabby.

In the same district, horses with white areas or flesh-coloured skin were also affected. The affected parts were scabby, especially the heels of the legs. The inspector states that the disease was due to aphides. At the same time he remarks that the food in the paddocks in which affected sheep were grazing was mainly trefoil. Sheep in paddocks where there was no trefoil were not affected. It always. occurs in the spring.

The stock inspector at Tamworth reports in August 1914," aphis. foot in horses is only seen in good seasons and when there is abun.­dance of trefoil. It affects the white parts of horses, mainly on the legs." It is of interest to note in connection with this report that in 1914, on account of the very dry season, there was no growth of trefoil in the Tamworth district and no aphis disease was seen.

Stock inspector at Meriwa reports that aphis disease is seen when there is a rank growth of trefoil in the spring and the plant is covered with aphis. It affects horses and cattle grazing over it.

The stock inspector at Merah North reports in August 1914 the o'ccurrence of aphis disease affecting- sheep and horses. In sheep the areas affected were the shorn parts, and the ears, nose, etc, In horses it attacked the white or pink skin.

The stock inspector at Warialda reports in August 1914 the occurrence of aphis disease, mainly in lambs, but also in adult sheep. horses, and cattle. The affected animals were grazing in paddocks where trefoil was abundant,

The stock inspector at Burren Junction in September 1914 reported that aphis disease was present. Horses were the principal sufferers but it had also appeared in sheep and cattle. The parts. affected were mainly around the mouth and nostrils.

The stock inspector at Scone states that aphis disease is par­ticularly seen in seasons when there is abundant growth of trefoiL In that district it affects horses with white skin on the nose or feet .. Occasionally it is seen in cattle.

In 1910 the stock inspector in another district drew attention to the fact that in his district, although in that year aphides were plentiful, there was no aphis disease.

In October 1911 Dr J. B. Cleland, of the Government Bureau of Microbiology, visited the Coonamblc district in connection with the occurrence of the aphis disease already mentioned, and reported to the Stock Department that the dermatitis was then on the decline. The animals chiefly affected were lambs, but it was also seen in some ewes. They were depastured on trefoil which was said to be infested' with aphides. The symptoms shown by the affected animals were a scabby formation on the ears accompanied by intense itching. The

1 I am indebted to Mr S. D. Symons, l\LR.C. V.S., Chief Inspector of Stock, New South 'ValeR, for permission to make use of the official records in connection with" aphis disease."

GENERAL ARTICLES. 49

same condition was seen along the back and the loins. The sheep had r~cently been shorn. Horses were also said to be affected, but only on white areas or the pink skin. Such horses were not stabled. The condition occurred always in the spring when clover (trefoil) was abundant and infested with aphides.

An amplification of this report is found in the Report of the New South Wales Government Bureau of Microbiology for I9I2, in an artiCle by Dr Cleland on An Outbreak of Dermatitis probably allied to fagopyrismus, the symptoms and incidence of the disease are again related; but it is also stated that when the disease was first seen at Gular, Coonamble district, in 191 I, trefoil, which is common in that part was quite green; when he observed it, however, the trefoil was dry and shrivelled up. Aphides were considered by the stock· owners to be the cause of the trouble.

Dr Cleland in his report does not specifically say whether he con­sidered the aphides were or were not the cause of the condition, but he remarks that the disease is in some way associated with sunlight and shows a close parallel to the condition known as fagop),rismus. In conclusion, he says that it is quite possible that in some way aphis-infested clover (trefoil) may sensitise animals feeding on it so as to render them sensible to sunlight; but, he adds, on the other hand, it may not be the aphis but some other factor which appears at the same time as the aphis.

Apparently from the report no definite opinion was formed as the result of the investigations as to the actual cause of the trouble.

In 1911 Mr Froggatt, Government Entomologist, published a pamphlet on Aphis Foot of Horses in the Tamworth District. The conditions he described are quite similar to those affecting horses in the so-called aphis disease in other localities. From a lesion on the hock of an affected horse he obtained an acarus, which he identified as chorioptes equi, and he therefore considered that the so-called aphis disease is in reality one of symbiotic acariasis.

Subsequent to investigations by me, about to be described, the stock inspector at Tamworth reported, 11th October 1915, that a considerable number of horses and cattle were affected with aphis disease or aphis foot. He also stated that owing to the good spring growth the herbage generally was covered with aphis, which were locally considered to be the cause of: the trouble. In reply to some specific questions relating to this report the inspector replied as follows :-

1. "The chief form of herbage attacked by the aphis is trefoil and wild mustard."

2. "I have never seen aphis on the skin of affected animals." 3. "The affected horses and cattle are depasturing on trefoil, wild

mustard, prairie grass, and variegated thistle." The following may be considered a summary of the information

compiled from the official records concerning the condition known as aphis disease:-

1. The disease mainly occurs in the spring. 2. At this period of the year both aphides and trefoil are abundant

as a rule. 3. The condition is only seen in animals feeding in trefoil paddocks. 4. Sheep, horses, and cattle are affected. Sheep are mainly affected

D

50 GENERAL ARTICLES,

soon after shearing, and the parts diseased in this case are along the back and loins, but the ears and nose may also be implicated. Horses and cattle are only affected upon" white" or unpigmented skin. (It may be noted here that the skin on the back of merino sheep is usually unpigmented.)

5. The symptoms observed by stock-owners are swelling of the skin, with reddening and exudation; scab formation; itching accom­panied by biting, scratching, or rubbing the parts; and the resultant formation of raw surfaces.

6. Practically all stock-owners are convinced that the cause is the aphis.

Investigations into the Cause of the so-called Aphis Disease. Towards the end of the spring of 1915 I was invited by the Chief

Inspector of Stock, Mr S. D. Symons, M.R.C.V.S., to investigate and endeavour to ascertain the cause of the so-called aphis disease. As the result of enquiries in different localities, the district of N arrabri was selected in which to commence operationg, and I visited it at the beginning of October.

Unfortunately a number of circumstances prevented my completely carrying out the programme as arranged. A gentleman who had considerable field knowledge of aphis disease had promised to take me to various places to inspect some affected animals, but was ill in bed on my arrival, and could render no assistance.

Although no time was lost in getting to work after news of the disease around N arrabri, yet on my arrival I found that the condition had practically disappeared for the season. It was the consensus of opinion among stock-owners that the disease had been very mild that season, because, they said, "the aphis were scarce this year." I also ascertained that although the spring had started well and the growth of herbage was promising the latter had rapidly dried up on account of want of rain.

The district within a radius of about 2 5 miles around N arrabri was well searched, but the attempt to discover fresh cases was unsuccessful. The enquiry, however, was not altogether fruitless, as by conversing with a large number of stock-owners one was able to get a pretty complete picture of the clinical features of the disease at first hand, although their observations and deductions were frequently, to say the least, confusing.

Some sheep with their ears and nostrils affected were discovered in a shearing shed waiting to be shorn. They were young animals, and the lesions were of some standing and healing up. They con­sisted of thick crusts, which appeared to be composed of dried blood and exudate, upon the marginal portions of the ears and around the nostrils. In one or two cases suppuration was evident.

I was also shown at other places where sheep had suffered a short time previously a horse and a young bull affected with aphis disease. The horse was stated to be continually rubbing its nose and had rendered that place quite raw. The animal had an unpigmented area (flesh mark) upon the nose, about a hand's-breadth in extent. This was intensely inflamed, and in places the skin was eroded. A number of different medicaments had, however, been applied, and consequently the lesion was masked.. .

GENERAL ARTICLES. 5 I

The young bull, a red and white animal, the back entirely white, had a superficial wound about 8 inches square upon its left hind­quarter in the region of the external angle of the ilium. This had recently scabbed over. It was such as could have been made by rubbing against some hard surface, or by biting the part. On the same side, but over the loins, the skin was thickened and partly covered with dry scabs. Here, again, various coloured medicaments had been applied, and rendered it very difficult to ascertain the real nature of the lesions.

On Sunday, whilst walking about the outskirts of the town of N arrabri, I observed in various places several young cattle with bare areas of greater or lesser extent upon the back, one or two of them showing distinct cicatricial tissue. All the affected areas had been covered with white skin. I ccmld not see anyone who was able to give me any information concerning these cattle, but it is highly probable that they had been affected with the disease and had recovered.

Careful inspection was made of a number of paddocks in which affected animals had been depastured, with the object of ascer­taining the flora. The main fodder at the time of inspection appeared to be trefoil. This was very abundant, but had become quite withered up except on some marshy and shady places by the river, where it was still green but not being grazed over. Aphides had disappeared from the locality. In connection with the trefoil re­maining green in certain places, it is interesting to note that the stock inspector at N arrabri, writing on 18th October concerning the obtaining of a further supply of trefoil, wrote: "I have noticed a few sheep which are running on the river frontages with sores on their ears which appear to be recent."

In the paddocks there was also a good deal of marsh mallow (malva rotundiflora and parviflora) and a variety of other plants, which, however, did not appear to be sufficiently numerous to warrant any detailed investigations at that stage of the work. Although specially sought for, no plants of polygonum or hypericum species could be found in the paddocks where affected animals had grazed.

The history obtained by me of the disease in the N arrabri district is substantially in agreement with that recorded from other localities. It occurs in the spring and disappears with the approach of summer, its greatest incidence being from August to October. All the domesticated herbivora are affected, but principally sheep. In horses and cattle only individuals with unpigmented skin show lesions. The majority of sheep show symptoms soon after being shorn, i.e., when the unpigmented skin of the back is no longer protected by a thick coating of wool. The ears and noses of sheep may also be involved.

The disease, at least as it affects the bodies of sheep, is coincident with the fresh and luxuriant growth of herbage; also with the shearing season and the appearance of aphides.

The history as to the time of the year the condition is seen in other animals is not so definite. Although the attention of stock­owners is apparently drawn to it in horses and cattle at the same period as when sheep are usually suffering, yet some accounts seem

GENERAL ARTICLES.

to convey the impression that the former animals may be affected at other times of the year, in that district at least, but principally during the spring.

Lesions.-The description here given of the lesions as seen in the field, particularly in the acute stages, is as related to me by various stock-owners, accounts of cases being ignored which obviously had no connection at all with aphis disease. It will be remembered that the cases seen by me were in an advanced stage, and recovering, or had recovered, from the disease.

The parts affected- appear to be invariably cutaneous. No lesions have been observed elsewhere, so far as could be ascertained.

The changes affect only unpigmented skin. Pigmented skin is apparently never affected. Furthermore, when such unpigmented skin is protected from the rays of the sun, as in the case of sheep by wool, or, when the wool is shorn off, by dirt or dark-coloured applications, it remains normal. The same has been observed when unpigmented areas of skin on horses have been smeared over with black substances, whether medicated or not.

In sheep the common sites of the lesions are on the back, ears, nostrils, and around the mouth. In horses common sites are the nose and lower parts of the extremities. I n cows the udder and the teats have occasionally been affected. Lesions may, however, occur in any situation where the skin is unpigmented and exposed to the sun's rays. As a rule the lesions on sheeps' backs are observed within a short time of being shorn. The first thing noticed is a marked reddening. Soon after, if the hand is run over it, the affected skin feels markedly swollen. Later there is an exudation of a fluid which coagulates and forms crusts or scabs. These crusts may dry up and fall off, leaving fresh normal skin underneath. Such a result is, however, apparently not the usual one. The more usual course is that, accompanying the inflammatory cedema, there is considerable itching of the affected skin. This causes the animal to bite, rub, or scratch the part, in consequence of which the lesions may become more extensive and serious. Larger or smaller areas may be quite denuded of hair or wool and epithelium, and present raw surfaces. The scabs of mixed blood and exudate forming over these surfaces may be of considerable thickness. Not infrequently these scabs are rubbed off again. In mild cases there may be only slight superficial erosions, but not infrequently complications arise owing to the entrance of pyogenic organisms into the wounds, with consequent suppuration and extension of the lesion.

In sheep, when the wool has well grown over the body again, the trunk lesions apparently disappear, and are not seen again until next shearing time.

According to my own observations, the lesions on the ears and nose are quite independent of shearing. As will be shown later, this is what one would expect, seeing that these parts are always exposed to the sunlight. The changes occurring on these areas are fundamentally of the same character as those on the back, viz., a marked erythema, foIlowed by an inflammatory redema, with exudation of plasma, which dries and forms a more or less thick crust. Scratching or rubbing the parts results in complications,

GENERAL ARTICLES. 53

e.g., raw bleeding surfaces subsequently covered by scabs of dried blood and exudate, or suppuration and ulceration. In the case of the ears of young sheep, however, dry necrosis of their tips is not at all infrequent. Sheep-owners informed me that it is quite a common thing for young sheep, especially young lambs, to have their ears" wither up." Many owners, however, do not appear to associate the lesions of the ears and nose with that of the back or aphis disease, and I could not get any reliable information locally as to whether these parts were affected at any time of the year or only during the spring. Chiefly. because the owners were so con­vinced that aphides were the cause of the disease, when speaking of the seasonal occurrence of the latter they could not or would not dissociate it from the former. Consequently, when they were apparently speaking of the disease I constantly found that they were in reality referring to the appearance and disappearance of the aphis. It is quite probable, however, that the lesions on the nose and ears are also most commonly seen in the spring, because the herbage is then green and fresh and the sheep are young.

The information collected concerning horses and cattle was also in accord with that already known. Every owner had no hesitation in saying that it was only the unpigmented areas of skin that were involved. Pigmented skin was never affected, except, perhaps, by extension due to complications, e.g., suppuration. Furthermore, a number of farmers informed me that by blackening the pink parts of the skin even these escaped; also that if sheep became covered with dust immediately after being shorn there were little or no signs of the trouble on the back.

Coincident with this special form of dermatitis in the spring around Narrabri aphides are usually very prevalen.t, being most plentiful upon trefoil, and the opinion is most tenaciously held that the aphis is the cause of the trouble. It was also said that when the aphides take wing the disease disappears, and that when ulceration appears it is the result of aphides laying their eggs in the lesions. Nevertheless, in spite of many enquiries, no one had ever seen aphides on the lesions or eggs in the eroded parts.

At N arrabri I ascertained that the conditions, as elsewhere, occurred exclusively in paddocks where trefoil was growing. In this district trefoil grows very luxuriantly in some paddocks, and in the spring forms a thick carpet of green, but it soon dries up under the influence of the hot sun, and at the time of my visit (October) many paddocks contained only dry brittle masses of stalks with an admixture of innumerable seeds, the latter forming a valuable food for sheep in the summer when the paddocks are quite dried up. In damp and shady places, however, the trefoil remains green for some time after the other has withered up and aphides have disappeared, and this fact enabled me to get a supply of green trefoil for experimental purposes.

Feeding and Control Experiments wt'tlt Trefoil (Medieago Dentieulata). As a result of the information collected, during my observations in

the N arrabri district, it was decided to conduct in the first place experiments with the common trefoil. Accordingly, arrangements were made for consignments of the fresh green plant to be forwarded

54 GENERAL ARTICLES.

regularly. It was examined carefully before being fed and found to be free from admixture with any other plants. It was quite healthy, no fungus or disease being detected by naked-eye examination, nor were any aphides present. Microscopic examination for fungi was not attempted owing to the great bulk of the material employed, and one could not be certain how much of the trefoil would have to be examined in order to satisfy criticism on this point. It was obviously impracticable to examine every portion of it with the microscope.

The experiments were divided into three series, viz. :-(A) Feeding guinea-pigs upon trefoil and at the same time expos­

ing them to the direct rays of the sun. (B) Feeding guinea-pigs upon trefoil but 'protecting them from

the direct rays of the sun. (C) Exposing guinea-pigs to the direct rays of the sun but feed­

ing them upon their ordinary diet containing no trefoil.

(A) Feeding Guinea-pigs upon Tn.lott and at the same time exposing tltem to tIle Direct Rays 0.1 the Sun.

For this experiment five full-grown guinea-pigs were used, the marks and numbers being as follows :-

No. 1. An albino, i.e., the entire skin was unpigmented. The hair was long but sparse, so that the pink skin was easily discernible underneath.

No.2. An albino. In this case the hair was short and thick, affording a complete covering to the body except the ears and to some extent the nose.

NO.3. Black and white. Ears and nose unpigmented. NO.4. Red and white. Nose and one ear unpigmented, the other

ear pigmented. NO.5. Red, black, and white. Nose and one ear unpigmented,

the other pigmented. Feeding was commenced on 5th October 1915. The animals

were fed exclusively upon fresh trefoil for twelve days, from 5th to 21st October inclusive, with an interval of five days, i.e., from 13th to 17th inclusive. The interval occurred owing to the supply of trefoil having run out. During that time the animals were fed upon grass only. There was no admixture with any other plants.

The total amount of trefoil consumed during the twelve days' feeding was 24! lbs., or 2 lbs. Ii ozs. daily. This gives a daily average per guinea-pig of about 7 ozs.

The five animals were fully exposed to direct sunlight during the experiment and for a week after its completion. During the period there were several days on which there was little or no sunshine, and on no occasion could the weather be said to be hot.

I Ith October. Sixth Day 0.1 Feeding. - Nothing unusual was observed until this day, when the unpigmented ears of all the animals appeared to be slightly erythematous.

On the same day the hair along the whole of one side of the body of No.2 was closely clipped off whilst the other was left protected by thick hair, the object being to have on one side somewhat similar conditions to those obtained in shorn sheep.

I2tlt October. Seventh Day.-Erythema of the unpigmented ears

GENERAL ARTICLES. 5S

was very marked. The edges and tips of the ears of No. I were, in addition, bleeding. In the same animal, on the right side of the back, about the region of the last rib, there was a small superficial erosion about the size of a lentil. It was also easy to note the reddening of the skin under the sparse hair. In the afternoon a bald patch, a little under I inch in diameter, had appeared around the eroded spot and the latter now presented a raw ulcerated surface about a quarter of an inch in diameter. In addition to the reddening, the skin on and around the depilated area was distinctly swollen. In several places on the swollen skin there were a number of lighter areas, as if wheals were beginning to form. When watched the animal was seen to bite frequently at the eroded surface on the back and to scratch its ears as if there were considerable cutaneous irritation.

NO.2. This animal showed no cutaneous alterations except erythema, but it was observed to be continually shaking its body like a wet dog, as if to remove some irritant.

I3tlt October. Eightlt Day.-Non-feeding interval commenced. No. 1. There were no fresh raw surfaces on the back and the

existing one had a scab over it of dried exudate and blood. There were also small dried points of yellowish exudate upon the intact swollen skin. The edges of the ears, however, were quite raw and had fresh dried blood on them in parts.

NO.2. The skin along the back where the hair had been clipped off appeared distinctly swollen. It was also markedly erythematous. On it was a small eroded area about an eighth of an inch in diameter, which had scabbed over during the night.

All the unpigmented ears of all the animals were very reddened, some having raw, bloody edges. The upper surfaces of the ears of Nos. 3 and 4 were covered with a dry, yellowish exudate. The pigmented ears were normal. The noses also of these two animals were red and swollen. On this day no signs of biting or scratching were observed until the animals had been exposed to the sun for about an hour, when No. I evinced signs of cutaneous irritation by biting vigorously at the raw surface on its back and rubbing its body against the cage. Both the depilated and the eroded surfaces had increased in extent, but there was no suppuration.

NO.2. Several small superficial wounds had appeared along the clipped back and there were a number of bead-like points of exudation.

NO.3. The upper surfaces of the ears were now quite raw, the skin having been torn off in large flakes by scratching. Some of these shreds were still hanging from the edges of the ears. The raw surfaces were covered with a clear, yellowish exudate. The eyelids were swollen and reddened and a small amount of dry, yellowish exudate was observed along the edges. The nose was red and swollen and showed a few pinhead points of exudate.

NO.4. The unpigmented ear was deeply reddened and freely desquamating. At mid-day all the animals showed considerable signs of itching of the unpigmented areas by scratching at the ears, back, or nose, and by continually shaking the body or head.

I6t1t and I7t1t October. Eleventh and Twelfth Days from the Commencement of Feeding __ Fourth and Fzjtlz Days of Interval.-The condition of the unpigmented areas of skin in all animals had

GENERAL ARTICLES.

progressed. The raw surfaces on Nos. I and 2 had increased in size, whilst some new ones had made their appearance. Two eroded areas, each about a quarter of an inch in diameter, were seen this day on the white skin of NO.3, in the region of the crest of the ilium. The affected skin of all animals had become markedly thickened.

Iff tIt October. Tltirteentlt Day from Commencement if Feeding.·­Re-commenced feeding with trefoil this day.

No. 1. The upper surfaces of both ears had become thickly covered with a crust composed of dried blood and exudate. Along the right side of the body, near the spine, there was a large raw surface about 4 by 1k inches in extent, which during the night became scabbed over but which was rendered raw again during the day by rubbing or biting.

NO.2. That part of the back from which the hair had been clipped still continued to show pinhead or larger points of exudate on the swollen skin. There was also on the same part of the skin a few areas of superficial erosion, the result of biting and scratching. These latter became scabbed over during the night, but the scabs were torn off during the day in the effort to relieve the irritation. The side of the body from which the hair was not clipped remained quite normal, save perhaps for a little erythema. There were no signs of irritation of that part.

NO.3. The upper surfaces of the ears were thickly covered with a crust of dried exudate and blood. The edges, however, had a necrotic, withered-up appearance. The rims of the eyelids were markedly inflamed and matted with a clear, yellowish exudate. The swelling and exudation of the nose appeared to be subsiding.

Nos. 4 and S. Inflammation, exudation, and irritation were marked in the unpigmented and unprotected parts, but the pig­mented and protected areas, including the ears, nose, etc., were quite unaffected.

19t1z to 21st October. Tentlt to Twelftlt Days of Actual Feeding / Fourteentlt to SixteentlzDays from tlte Commencement.-In all animals the lesions had still progressed. The eroded surfaces had increased in size, and a number of fresh ones had made their appearance. Irritation of the skin was still marked, shown by shaking the body and scratching and biting various parts. The unpigmented ears of all animals were thickly encrusted with dried blood and exudate. In two cases the skin was hanging from them in shreds. In both ears of NO.3 and in the unpigmented ear of NO.4 dry necrosis of the tips and edges was marked.

On 22nd October the feeding of trefoil was discontinued and the animals reverted to their usual food. After a few days from the discontinuance of the trefoil the animals began to recover. The signs of cutaneous irritation began to subside rather rapidly. Lesions gradually commenced. to heal up, and the scabs which formed on the raw surfaces during the night ceased to be rubbed off during the day. No secondary infection of these places occurred, the scabs gradually dropping off and leaving fresh epithelium underneath. Where no scabs had formed on the affected skin there was marked desquamation. In the case of guinea-pig No. I the lesions, on account of their extent, took over a month before they had healed. Progress, however, was uninterrupted in all animals except

GENERAL ARTICLES. 57

NO.3. Here the necrotic portions of the ears gradually dropped off, leaving behind little more than the stumps.

For about a month the affected ears of all animals continued to show a branny desquamation.

The animals were exposed to the sun during the period of recovery, just as they were during the period of feeding trefoil.

(B) Feeding Guinea-pigs upon Trefoil for the same Period and 012

the same Amount per Head as in Experiment (A), but not exposing them to Direct Rays of tile Sun.

For this experiment three animals were employed, viz., two albinos and one white and red with an unpigmented nose but pigmented ears. An albino guinea-pig was born in the same cage a few days after the feeding was commenced. The room in which the animals were kept was well lighted, but by diffuse, not direct, sunlight.

The result of this experiment was that the animals remained quite normal. There were no signs of irritation of the skin, and no reddening or swelling of any of the unpigmented parts. Even the young animal showed no reaction after ingesting the trefoil.

(C) Animals exposed to Direct Sunlight, but at the same Time fed upon their Ordinary Diet containing no Trefoil.

In this control experiment six guinea-pigs were used, viz., five albinos and one red and white. It was carried out subsequently to the foregoing experiments in order that no error in feeding the various animals should arise. Although during the period of three weeks in which they were exposed to the sun there were more sunny days, and it was perceptibly hotter, yet these animals showed no signs of reaction whatever, i.e., the skin showed no signs of inflamma­tion, exudation, or irritation.

Summary of Results of Experiments. The feeding of guinea-pigs upon an exclusive diet of trefoil, and

exposing them at the same time to direct sunlight, resulted in erythema and inflammatory cedema of the skin, i.e., reddening and swelling of the skin, accompanied by exudation of plasma. The changes taking place induced a more or less severe pruritus and other lesions, the consequence of scratching, etc., varying in degree and extent according to the intensity of the irritation, from mere depilation and slight scratches to large areas from which the whole of the skin had been forcibly removed.

Only unpigmented skin was affected, and apparently when such skin is protected from the sun, e.g., by a thick covering of hair, even it may escape.

As a result of the exudation, crusts composed of dry exudate often formed on the affected skin. If the skin had become broken, by biting, scratching, etc., then large crusts or scabs of dried blood and exudate were formed. Necrosis of the tips of the ears occurred also in two animals. The irritation appeared to be considerably diminished, even if it did not cease, during the night, but it returned in all its intensity soon after the animals were again exposed to direct sunlight.

58 GENERAL ARTICLES.

As just noticed, the primary lesions visible to the naked eye were erythema and inflammatory cedema of the skin with exudation. The subsequent injuries to the skin, e.g., erosions, ulceration, etc., were secondary.

When experimentally induced, as in the foregoing, the symptoms set in about six days after the commencement of feeding, and it appears that a relatively considerable amount of trefoil must be consumed before such symptoms do appear. Symptoms do not disappear at once after the stopping of trefoil as fodder, but continue in diminishing intensity for a few days and then disappear rather rapidly. It would thus appear that the agent responsible for the condition is eliminated fairly quickly from the system. Lesions resulting from biting, etc., persist for a longer or shorter period according to their degree.

The second experiment shows that when a similar type of animal, i.e., one with unpigmented skin, is fed upon the same amount of trefoil and for the same period, but protected from the direct rays of the sun, no reaction takes place, even in a very young animal. It indicates that in addition to the ingestion of trefoil there must at the same time be exposure to the direct rays of the sun before reaction, will occur even in unpigmented skin.

The third and control experiment shows that animals with unpigmented skin exposed to the direct rays of the sun, but not fed upon any sensitising agent, do not exhibit the pathological reactions presented by similar animals that have ingested trefoil under the same conditions.

General Conclusions. The condition produced in guinea-pigs by feeding them upon

trefoil is in all respects similar to the disease affecting sheep, horses, and cattle in certain districts and popularly known as aphis disease. This disease is not due to aphides, but to feeding mainly or ex­clusively upon the common trefoil (medicago denticulata).

In the cases investigated the condition was not due to polygonum or hypericum species of plants contaminating the trefoil, as none of these were present in the fodder used in the feeding experiments. N or were they seen in paddocks where affected animals had grazed.

The affection in sheep, horses, and cattle is primarily a dermatitis involving the unpigmented areas. Even in the pigmented parts lesions do not occur if such parts are protected from the direct rays of the sun. This will explain why the backs of sheep become affected soon after being shorn, and not before. Protection may also be afforded by a thick coating of hair, by keeping susceptible animals, that is those with unpigmented skin, in the shade, or by covering the pink skin with soml'! dark substance, such as walnut juice, solution of permanganate of potash or logwood, or even lampblack mixed with grease.

The wide spreading lesions with thick crusts of dried blood and exudate upon them are the indirect result of the ingestion of trefoil, but directly due to biting, scratching, or rubbing the parts in consequence of pruritus.

The affection of the nose and ears, including the necrosis of the latter in young sheep, is also due to the ingestion of trefoil.

GENERAL ARTICLES. 59

The factors necessary before the condition can set in appear to be the following:-

1. The food must consist entirely or mainly of trefoil. 2. The animal must possess unpigmented skin. 3. Such unpigmented skin must be exposed to the direct action of

the sun's rays. So far as the food is concerned, trefoil (medicago denticulata) is a

common plant in New South \Vales, and is commonly eaten by stock, but not in large quantity, except in those localities where this special form of dermatitis occurs. It is apparent that the ingestion of small amounts of trefoil has no injurious effects. The exciting agent is, as shown by the experiments, eliminated fairly rapidly from the system. In the Narrabri district it was generally admitted by stock-owners that the more trefoil present the worse was the disease.

With regard to the particular kind of skin affected, the experi­ments corroborate what has been observed in the field, viz., that only those parts in which the skin is unpigmented are affected.

Furthermore, the areas involved are those always exposed to the direct rays of the sun-nose, ears, back, etc. In sheep the condition as it affects the back is only observed after the wool has been removed by shearing. It is therefore evident that the thick covering of wool acts as an efficient protection to the unpigmented skin underneath. As regards the nose and ears of sheep, it has been shown that these parts are affected independently of shearing. This is to be expected, as they have no thick covering of wool. It is, however, quite probable that even lesions in these areas are most common in spring, for reasons already advanced. It is also., possible that at other times of the year either the active agent disappears with the drying up of the plant, or that the dried trefoil then usually only forms a moderate proportion oi the animals' diet.

CONDITIONS SIMILAR TO THAT OF TREFOIL DERMATITIS.

F agopyrismus. This is a dermatitis resulting from the ingestion of buckwheat

(polygonum fagopyrum and polygonum persicaria) in conjunction with the action of sunlight upon unpigmented skin. The degree of cutaneous reaction is said to depend upon the intensity of the sun's rays and the amount of buckwheat ingested. It is considered that the green flowering plant is the most active, but the disease may also follow upon the ingestion of the grain, straw, chaff, or bran.

In the case of fagopyrism us it is known that animals with no unpigmented areas of skin remain unaffected, as do also those in which the unpigmented parts are blackened over; and that those animals in which the unpigmented parts are covered by dirt or dust are less severely affected. (Compare the observations of farmers in connection with trefoil dermatitis.) Furthermore, no cutaneous reaction is observed even in white animals if buckwheat is given in cloudy weather, or in localities protected from direct sunlight.

In buckwheat exanthema exposure need not be, made to the sun immediately after feeding on buckwheat, as it may follow three or four weeks after plentiful feeding upon that plant.

60 GENERAL ARTICLES.

In experiments made upon white mice and guinea-pigs it was found that the buckwheat lost its toxic properties on extraction with alcohol, and that the extract was toxic to white animals exposed to sunlight.

In fagopyrismus the lesions appear mostly upon the face, ears, nose, and throat.

There are two main views as to the cause of this condition, viz. :­I. That it is due to fungi in the buckwheat which come in contact

with the skin and injure its unpigmented parts, either directly or by their toxins.

2. That the cutaneous reaction is produced by toxins which circulate in the blood. These toxins injure the vaso-motor nerves under the influence of the chemical rays of the sun in areas in which such influence is not prevented by pigmentation, and such injury is followed by changes in the vessel walls.

The same toxins are also considered to be the cause of nervous and digestive disturbances.

In mild cases there is an intense erythema, accompanied by slight swelling, hypersensitiveness, and itching of the affected parts, and followed by desquamation. In severe cases there is an intense, cedematous inflammation, often with vesiculation of the parts mentioned. A n exudate appears on the surface, dries, and forms scabs or crusts, accompanied by violent itching. Brain symptoms are common, and the appetite is diminished. Death may result after eight to twelve hours; but, as a rule, recovery takes place in a few days, especially if the animal is placed in a cool, shady situation soon after the onset of symptoms.

Clover Disease. This condition has been described by several observers as occur­

ring on the continent of Europe, but it does not appear to have been recorded elsewhere.

The disease is stated to consist in inflammation of the white portions of the head and limbs. Frequently the mouth is involved and systems of systemic disturbance have sometimes been noticed. The condition has especially been seen in horses after generous or exclusive feeding on Swedish clover (trifolium hybrid urn ), and also on red clover (trifolium pratense). It has also been observed in cattle and sheep after pasturing on clover meadows or feeding on red clover.

The cause appears to be unknown. One view is that it is due to the ingestion of fungi with the clover, and another that clover produces a somewhat similar effect upon the body to that caused by buckwheat. The symptoms appear to be parallel with those seen in trefoil dell"matitis in New South Wales, viz., in mild cases an erythema with moderate swelling of the unpigmented areas of the skin, followed by desquamation of the affected areas. In cattle the udder may be affected. In severe cases the unpigmented areas are intensely reddened. This is accompanied by swelling and tenderness of the parts, and sometimes followed by vesiculation in places. Then a yellowish exudate appears, which soon dries upon the skin and forms scabs.

Pus formation may take place in the scabbed areas.

GENERAL ARTICLES. 6{

One or two observers have noticed itching and inflammation of the hair bulbs. In some cases, dry necrosis of the affected portions have followed, and a purulent conjunctivitis has been noted in some instances.

The condition has been attended with fatal results in some cases where severe nervous and digestive disturbances have been in evidence.

I am unable to ascertain whether any feeding experiments were made or not in connection with" clover disease" in order to find out definitely whether the cause lay in the clover itself, or in plants or weeds growing with it.

Cutaneous lesions have been recorded as appearing in cattle after feeding on large quantities of green lucerne (medicago sativa), especially when it is young. The main symptoms consist in redden­ing and swelling of the skin, with vesiculation. A copious exudate appears on the skin and dries into crusts. Pus may form under the scabs, and there is always considerable tenderness. The abstract, however, from which this note is taken makes no mention of the pigmented ·or unpigmented condition of the affected areas in the cattle. When horses are affected the skin and mucous membranes of the mouth may be attacked simultaneously, or only those parts of the limbs covered with white hair are involved. The symptoms are inflammatory cedema of the affected skin, with exudation of a sticky fluid, followed by scab formation.

Recently, an interesting article has been written by Rogers on The Action of St. John's Wort as a Sensitising Agent for Un­pigmented Skin. The condition is apparently analogous to that produced by the ingestion of trefoil. Only unpigmented areas of skin are affected, and those parts only upon exposure to direct sunlight. The symptoms also are very like those observed in connec­tion with trefoil dermatitis, viz., reddening and swelling of the unpigmented skin. In sheep and goats the ears and eyelids are common seats of the lesions. Whether there is any accompanying irritation of the affected parts in these animals is not stated.

In horses also the unpigmented areas are the parts affected. Here there is acute itching, as a result of which the animal bites or rubs the parts until the skin is excoriated. The lesions may subsequently become invaded by bacteria. It is stated that a common sequel to poisoning by hypericum in sheep in Algiers is loss of sight. In some animals there appears to be considerable systemic disturbance, which may result in death.

In the case of sensitisation by hypericum species, a definite fluorescent substance which is considered to be the sensitising agent has been isolated from the plant.

Rogers points out the similarity of the reactions in hypericum sensitisation and in other plants, viz, buckwheat, lucerne, and clover, when they are fed to animals under certain conditions, and appears to suggest that there is a probability of these fodder plants having a proportion of St. John's wort (hypericum species) mixed with them. In the case of the experiments recorded in this article, however, the trefoil was quite uncontaminated with any other plant. Furthermore, as already stated, in my investigations in the field at

62 GENERAL ARTICLES.

Narrabri special search was made for any plants of hypericum or polygonum species in the paddocks whence came affected animals, but without success.

BIBLIOGRAPHY.

(I) Adami, J. G.: Principles of Pathology. "The Skin," Vol. II. (2) Department of Agriculture, (Stock Branch) N.S.W.: Official Records. (3) Cleland, J. B.: Report of Bureau of Microbiology, N.S.W., 1912.

(4) Rogers, T. B.: St. John's Wort as a Sen sit ising Agent," American Veterinary Review, No.2, Vol. XLVI.

(5) Hutyra and Marek: Special Pathology and Therapeutics of the Domestic Animals. " Diseases of the Skin," Vol. II.

(6) Friedberger and Frohner: Veterinary Pathology. "Skin Diseases," Vol. I.

(7) Law, J.: Veterinary Medicine, Vol. IV.

JOHNE'S DISEASE. l

THE EXPERIMENTAL TRANSMISSION OF THE DISEASE TO CATTLE, SHEEP, AND GOATS, WITH NOTES REGARDING THE OCCUR­RENCE OF NATURAL CASES IN SHEEP AND GOATS.

(From the Research Laboratory, Royal Veterinary College, London.)

By Sir JOHN M'FADYEAN, M.B., B.Sc., LL.D., and A. L. SHEATHER, B.Sc., M.R.C.V.S.

THE purpose of the present article is to describe a number of experiments in which it was sought to infect animals with Johne's disease. The details of each experiment will be found in the record which forms the major part of the article, and only the more important results will be summarised and discussed here.

The experiments were begun over four years ago, and the main objects in view were ( I ) to follow the course of the disease from the moment of infection onwards, (2) to ascertain .whether inoculation or so-called "vaccination" with tubercle bacilli would confer any protection against J ohne's disease, and (3) to provide infected animals on which to study methods of diagnosis, particularly during the incubative or latent stage of the disease.

The facts with regard to the third of these objects have been o mitted from the present article, because it is intended to deal with that part of the subject in a separate report.

Dealing in the first place with the results of the experiments in respect of success or failure, it has to be noted as a remarkable fact that in the majority of cases the attempt to infect with J ohne's disease failed, as judged by the symptoms exhibited during life and

1 The experiments described in this article were carried out by the aid of a grant from the Board of Agriculture and Fisheries.