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The treatment of tuberculous cervical adenitis by intraglandular injections of Gelatin, Acriflavine, Calcium Chloride (GACC)
The Treatment of Tuberculous Cervical Adenitis by Intraglandular Injections of Gelatin, Acriflavine, Calcium Chloride (GACC) By R. A. HUNTER
From the Sanatorium, Bridge of Weir, Renfrewshire INTRODUCTION Although the incidence of tuberculous cervical adenitis has declined, yet many cases are met with presenting the stigmata of the condition, namely discharges, swellings, and disfiguring scars. Scarring is mainly of two types, first, the more offensive cicatrices due to the formation of pus and its subsequent discharge through the skin-a mishap which aspiration is by no means certain to prevent ; and secondly, the much less displeasing scars resulting from surgical interference which has as its objective the excision of the gland prior to pus formation, or whilst the gland capsule remains intact. To secure the early regression of these enlarged glands is, therefore, to reduce the liability of pus formation with consequent disfigurement, and at the same time to obviate a prolonged stay in hospital or a loss of educational facilities. A considerable amount of work, both experimental and clinical, has been clone in this Sanatorium employing a medium composed of gelatin, acriflavine, and calcium chloride (GACC) for intrapulmonary injections in tuberculosis (Hunter and Peill, 1938 ). A previous study, employing the same medium on the Jensen rat sarcoma (Hunter, i936), showed that these rapidly growing tumours were subverted by injections of GACC, and histologically it was found that the parenchyma of the tumour was hyalinized and calcified. The vessels were particularly affected, and it was suggested that this may play a big part in the disappearance of the tumour 'as it would tend to restrain or even prevent the circulation of blood and lymph in the parenchyma'. The growths rapidly regressed under treatment and in many cases completely disappeared.
Fig. I. Section obtained from hard body expressed from caseous cervicalglandshortlyafter treatment with GACC. Histologically it was composed of hyaline material heavily impregnated with calcium deposit. The calcified tissue appears black ; von Kossa's method. This case was treated a few years ago and is not one of the series reported. (• 2.)
I62
TUBERCLE
January i939
It was decided to treat tuberculous glands in the same manner in the hope that similar end-results might be obtained (Fig. I ). Only a total of 21 cases was available, but the results appeared to be sufficiently satisfactory to warrant a note on the subject. S E L E C T I O N OF CASES O f these 2I cases only 13 caused definite or gross alteration in the contour of the neck and measured (with calipers) over 35 ram. in diameter. In 9 of these 13 therewas obvious scarring from previous cervical abscesses. Direct films of the pus in five of these cases had shown tubercle bacilli, but in three others no evidence of tuberculosis had been elicited apart from the cheesy appearance of the pus. Pathological reports on the ninth case were not available. The remainder (8) of the 21 cases presented glands more than 2o mm. in diameter, but caused no visible alteration in the symmetry of the neck. O f this group one has scars said to be due to adenitis, but no pathological report was available. M E T H O D OF T R E A T M E N T The composition of the medium employed (gelatin, acriflavine, and calcium chloride) is described fully in a recent article by Hunter and Peill (I938), together with the method of preparation, the only difference being that a 5 per cent gelatin was used instead of a 3 ~ per cent solution. Immediately before use, the bottle containing the GACC was placed in warm water to melt the gelatin. A sterile i c.c. Record syringe and hypodermic needle (gauge I4) were used for the injection, which was given while the inoculum was at blood heat. The skin over the gland was cleansed with ether methyl, as a colourless antiseptic was preferred. The patients, aged'3-I 7 years, stood and turned their necks to a convenient angle to allow the fixation of the gland between the operator's finger and thumb when the injection was made. The dosage varied from o. 3 c.c.-o. 5 c.c. A small amount of GACC was left in the syringe to sterilize the needle track on withdrawal. No dressing was employed, and the children proceeded forthwith to their normal occupations at a residential school in the country. It was noted that there was no constitutional reaction. There was frequently a transient increase in the size of the gland and, in a few cases, reddening of the skin. The larger doses (o. 4 o- 5 c.c.) were particularly liable to produce the latter effect, and were discontinued. No further injection was given into any area showing local reaction until it had subsided. Further, it was considered desirable to inject the periphery of the gland before the deeper areas, so that a firm barrier between the greater part of the gland and the skin might be induced as soon as possible. Hardening of the gland was usually first appreciable within three to five days after the injection and was easily detected by the resistance offered to the needle when the procedure was repeated in neighbouring areas. The optimum dosage appeared to be o. 3 c.c. per injection daily, or every two or three days, and given at different situations into the gland, all depending on its size and condition. It is also suggested that after introducing the medium at about six sites, and provided the gland ceases to enlarge and soften, the injections be arrested until no further reduction in size has been appreciable for a fortnight before subjecting the patient to further injection.
January
1939
TUBERCLE
16 3
RESULTS The results obtained in the group of 13 cases with glands over 35 mm. in diameter were as follows, viz. : Four glands completely disappeared. Three glands showed only a small nodule not sufficiently large to be measured. Two glands regressed to approximately 9 mm. in diameter, leaving a fiat hard nodule. One gland is still causing alteration in the contour of the neck one month after cessation of treatment ; it continues to subside. Pus formation occurred only in the three remaining cases, in two of which the glands had been large and very soft when first observed. Smal{,incisions were made and typical cheesy pus was evacuated. In two instances tubercle ' bacilli were recovered ; one healed by first intention. In the third case no micro-organism was found in the pus and the wound closed in a few days. O f these three cases, two showed scarcely visible scars and no school time was lost. Injections were continued on the remaining adenitis, which is subsiding. O f the group of eight cases presenting glands of more than 2o ram. in diameter : Four glands have completely disappeared. Three glands have become insignificantly small. One gland has regressed to approximately io mm. Pus formation did not occur in any instance in this group. T H E T R E A T M E N T OF S M A L L C E R V I C A L GLANDS IN HEALTHY CHILDREN It was conceived that it would also be valuable to determine the reaction of small glands, not necessarily tuberculous, to the treatment. If these small glands reacted unfavourably, then a similar result might be expected in larger and more diseased glands. It was also felt that the smaller gland would more surely indicate the tolerance for, or reaction to, the treatment. Accordingly, all the available healthy children with a small degree of adenitis (IO-2O mm. in diameter), and possibly tuberculous in origin, were given 2- 5 injections of GACC over a period of two to four weeks. Six weeks after treatment the glands were harder and definitely smaller in i i cases, and had completely disappeared in 17 cases. In one case involving the posterior triangle there was no change, and it is significant that this was the only patient with enlarged or septic tonsils. One cannot escape the conclusion that a number of these glands would inevitably have made further progress without treatment. They were at a stage, moreover, when the parent or guardian would be reluctant to permit operative interference as not yet being worth while. In a few weeks' time, or when the matter comes up for consideration, it may be too late. It is much more satisfactory to give one or two injections into the gland, arrest growth, and obviate surgical or other scars, however slight. It is obviously more important to prevent growth than to take drastic steps for its removal ; in districts where cases of tuberculous cervical adenitis are fairly common, carefifl watch should be kept for small glands, and a few injections of GACC given without delay. It is recognized that the number of cases treated is small. Nevertheless, the results have been so encouraging that no apology is made for introducing the method to any who may care to give it an extended trial, which would, I believe, justify its acceptance.
164
TUBERCLE
January I939
SUMMARY (I) All the available cases (2i) of tuberculous cervical adenitis above 2o mm. have been treated by intraglandular injections of GACC, obtaining regression in 2o cases without loss of school time. Bilateral involvement was found in a few cases, and they responded satisfactorily to treatment. In only three cases is there scarring, in two of which the scars are difficult to detect. (2) All the available cases (29) of slight adenitis below 2o mm., and possibly tuberculous, have received an average of three injections each of GACC. A favourable response was obtained in 28 cases. This method appeared to inhibit further hyperplasia ; it holds out great promise in the prevention or treatment of cervical adenitis. I have to thank Dr A. J. Rae for administering the treatment and furnishing the necessary data. I also wish to thank Dr E. J. Peill, late Medical Superintendent, for facilitating this work. REFERENCES Hunter, R. A., and Peill, E.J. (I938) Brit. J. Tuber., xxxu, i36. Hunter, R. A. (I936) J. Path. Bact., XLIn, 35.
From the Sanatorium, Bridge of Weir, Renfrewshire INTRODUCTION Although the incidence of tuberculous cervical adenitis has declined, yet many cases are met with presenting the stigmata of the condition, namely discharges, swellings, and disfiguring scars. Scarring is mainly of two types, first, the more offensive cicatrices due to the formation of pus and its subsequent discharge through the skin-a mishap which aspiration is by no means certain to prevent ; and secondly, the much less displeasing scars resulting from surgical interference which has as its objective the excision of the gland prior to pus formation, or whilst the gland capsule remains intact. To secure the early regression of these enlarged glands is, therefore, to reduce the liability of pus formation with consequent disfigurement, and at the same time to obviate a prolonged stay in hospital or a loss of educational facilities. A considerable amount of work, both experimental and clinical, has been clone in this Sanatorium employing a medium composed of gelatin, acriflavine, and calcium chloride (GACC) for intrapulmonary injections in tuberculosis (Hunter and Peill, 1938 ). A previous study, employing the same medium on the Jensen rat sarcoma (Hunter, i936), showed that these rapidly growing tumours were subverted by injections of GACC, and histologically it was found that the parenchyma of the tumour was hyalinized and calcified. The vessels were particularly affected, and it was suggested that this may play a big part in the disappearance of the tumour 'as it would tend to restrain or even prevent the circulation of blood and lymph in the parenchyma'. The growths rapidly regressed under treatment and in many cases completely disappeared.
Fig. I. Section obtained from hard body expressed from caseous cervicalglandshortlyafter treatment with GACC. Histologically it was composed of hyaline material heavily impregnated with calcium deposit. The calcified tissue appears black ; von Kossa's method. This case was treated a few years ago and is not one of the series reported. (• 2.)
I62
TUBERCLE
January i939
It was decided to treat tuberculous glands in the same manner in the hope that similar end-results might be obtained (Fig. I ). Only a total of 21 cases was available, but the results appeared to be sufficiently satisfactory to warrant a note on the subject. S E L E C T I O N OF CASES O f these 2I cases only 13 caused definite or gross alteration in the contour of the neck and measured (with calipers) over 35 ram. in diameter. In 9 of these 13 therewas obvious scarring from previous cervical abscesses. Direct films of the pus in five of these cases had shown tubercle bacilli, but in three others no evidence of tuberculosis had been elicited apart from the cheesy appearance of the pus. Pathological reports on the ninth case were not available. The remainder (8) of the 21 cases presented glands more than 2o mm. in diameter, but caused no visible alteration in the symmetry of the neck. O f this group one has scars said to be due to adenitis, but no pathological report was available. M E T H O D OF T R E A T M E N T The composition of the medium employed (gelatin, acriflavine, and calcium chloride) is described fully in a recent article by Hunter and Peill (I938), together with the method of preparation, the only difference being that a 5 per cent gelatin was used instead of a 3 ~ per cent solution. Immediately before use, the bottle containing the GACC was placed in warm water to melt the gelatin. A sterile i c.c. Record syringe and hypodermic needle (gauge I4) were used for the injection, which was given while the inoculum was at blood heat. The skin over the gland was cleansed with ether methyl, as a colourless antiseptic was preferred. The patients, aged'3-I 7 years, stood and turned their necks to a convenient angle to allow the fixation of the gland between the operator's finger and thumb when the injection was made. The dosage varied from o. 3 c.c.-o. 5 c.c. A small amount of GACC was left in the syringe to sterilize the needle track on withdrawal. No dressing was employed, and the children proceeded forthwith to their normal occupations at a residential school in the country. It was noted that there was no constitutional reaction. There was frequently a transient increase in the size of the gland and, in a few cases, reddening of the skin. The larger doses (o. 4 o- 5 c.c.) were particularly liable to produce the latter effect, and were discontinued. No further injection was given into any area showing local reaction until it had subsided. Further, it was considered desirable to inject the periphery of the gland before the deeper areas, so that a firm barrier between the greater part of the gland and the skin might be induced as soon as possible. Hardening of the gland was usually first appreciable within three to five days after the injection and was easily detected by the resistance offered to the needle when the procedure was repeated in neighbouring areas. The optimum dosage appeared to be o. 3 c.c. per injection daily, or every two or three days, and given at different situations into the gland, all depending on its size and condition. It is also suggested that after introducing the medium at about six sites, and provided the gland ceases to enlarge and soften, the injections be arrested until no further reduction in size has been appreciable for a fortnight before subjecting the patient to further injection.
January
1939
TUBERCLE
16 3
RESULTS The results obtained in the group of 13 cases with glands over 35 mm. in diameter were as follows, viz. : Four glands completely disappeared. Three glands showed only a small nodule not sufficiently large to be measured. Two glands regressed to approximately 9 mm. in diameter, leaving a fiat hard nodule. One gland is still causing alteration in the contour of the neck one month after cessation of treatment ; it continues to subside. Pus formation occurred only in the three remaining cases, in two of which the glands had been large and very soft when first observed. Smal{,incisions were made and typical cheesy pus was evacuated. In two instances tubercle ' bacilli were recovered ; one healed by first intention. In the third case no micro-organism was found in the pus and the wound closed in a few days. O f these three cases, two showed scarcely visible scars and no school time was lost. Injections were continued on the remaining adenitis, which is subsiding. O f the group of eight cases presenting glands of more than 2o ram. in diameter : Four glands have completely disappeared. Three glands have become insignificantly small. One gland has regressed to approximately io mm. Pus formation did not occur in any instance in this group. T H E T R E A T M E N T OF S M A L L C E R V I C A L GLANDS IN HEALTHY CHILDREN It was conceived that it would also be valuable to determine the reaction of small glands, not necessarily tuberculous, to the treatment. If these small glands reacted unfavourably, then a similar result might be expected in larger and more diseased glands. It was also felt that the smaller gland would more surely indicate the tolerance for, or reaction to, the treatment. Accordingly, all the available healthy children with a small degree of adenitis (IO-2O mm. in diameter), and possibly tuberculous in origin, were given 2- 5 injections of GACC over a period of two to four weeks. Six weeks after treatment the glands were harder and definitely smaller in i i cases, and had completely disappeared in 17 cases. In one case involving the posterior triangle there was no change, and it is significant that this was the only patient with enlarged or septic tonsils. One cannot escape the conclusion that a number of these glands would inevitably have made further progress without treatment. They were at a stage, moreover, when the parent or guardian would be reluctant to permit operative interference as not yet being worth while. In a few weeks' time, or when the matter comes up for consideration, it may be too late. It is much more satisfactory to give one or two injections into the gland, arrest growth, and obviate surgical or other scars, however slight. It is obviously more important to prevent growth than to take drastic steps for its removal ; in districts where cases of tuberculous cervical adenitis are fairly common, carefifl watch should be kept for small glands, and a few injections of GACC given without delay. It is recognized that the number of cases treated is small. Nevertheless, the results have been so encouraging that no apology is made for introducing the method to any who may care to give it an extended trial, which would, I believe, justify its acceptance.
164
TUBERCLE
January I939
SUMMARY (I) All the available cases (2i) of tuberculous cervical adenitis above 2o mm. have been treated by intraglandular injections of GACC, obtaining regression in 2o cases without loss of school time. Bilateral involvement was found in a few cases, and they responded satisfactorily to treatment. In only three cases is there scarring, in two of which the scars are difficult to detect. (2) All the available cases (29) of slight adenitis below 2o mm., and possibly tuberculous, have received an average of three injections each of GACC. A favourable response was obtained in 28 cases. This method appeared to inhibit further hyperplasia ; it holds out great promise in the prevention or treatment of cervical adenitis. I have to thank Dr A. J. Rae for administering the treatment and furnishing the necessary data. I also wish to thank Dr E. J. Peill, late Medical Superintendent, for facilitating this work. REFERENCES Hunter, R. A., and Peill, E.J. (I938) Brit. J. Tuber., xxxu, i36. Hunter, R. A. (I936) J. Path. Bact., XLIn, 35.