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Treatment of acrodermatitisenteropathica by intravenous amino acid hydrolysate
Volume 82 Number 1
conductive hearing loss. In 1960, tympanotomy on the left revealed absence of the stapes and part of the incus. Subsequently, a Lempert-type fenestration procedure was performed. DISCUSSION The only unequivocal signs of ectodermal dysplasia in the present series are hypodontia and malformed teeth. Anomalies of the hair, skin, and nails were not present. T h e dental signs, in the J. pedigree at least, suggest that they are further examples of the EEC syndrome. T h e bilateral hypodontia and its presence in both maxilla and mandible makes it unlikely to be associated with the unilateral cleft palate anomalies. SUMMARY
The association of conductive hearing loss with the E E C syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip-palate) is decribed in one sporadic case and in a pedigree with four cases in three generations. Hypodontia was demonstrated in two and conductive hearing loss in three of the family members; in one of them there was congenital absence of the stapes and part of the incus.
Treatment of acrodermatitis enteropatbica by intravenous amino acid
bydrolysate S. Freier, M.B.,* J. Faber, M.D., R. Goldstein, Ph.D., and M. Mayer, Ph.D., Jerusalem, Israel From the Pediatric Gastroenterology Research Unit, Shaare Zedek General Hospital, and the Department o[ Clinical Biochemistry, Hebrew University-Hadassah Medical School. ~Reprint address: Pediatric Gastroenterology Research Unit, Shaare Zedek General Hospital, P.O. Box 293, Jerusalem, Israel.
Brie[ clinical and laboratory observations
1 09
The authors would like to thank Dr. B. W. Tanton for his assistance with the preparation of this paper, and the Departments of Pediatrics, Audiology, and Human Genetics of the University of Groningen for perusal of the case history of Case 1. We would also like to thank Dr. David W. Smith for drawing our attention to the recent publications of the EEC syndrome. REFERENCES
1. Coekayne, E. A.: Cleft palate, hare lip, dacryocystitis, and cleft hand and feet, Biometrika 28; 58, 1936. 2. Walker, J. C., and Clodius, L.: The syndromes of cleft lip, cleft palate and lobster-claw deformities of hands and feet, Plast. Reconstr. Surg. 32" 627, 1963. 3. Riidiger, R. A., Haase, W., and Passarge, E.: Association of ectrodactyly, ectodermal dysplasia, and cleft llp-palate: The EEC syndrome, Am. J. Dis. Child. 120: 160, 1970. 4. Bixler, D., Spivack, J., Bennett, J., and Christian, J. C.: The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome: Report of 2 cases and review of the literature, Clin. Genet. 3: 43, 1971. 5. Wildervanck, L. S.: Perceptive deafness associated with split-hand and foot, a new syndrome? Acta Genet. 13: 161, 1963. 6. Birch-Jensen, A.: Congenital deformities of the upper extremities, Copenhagen, 1949, Ejnar Munksgaards Forlag. 7. Berndorfer, A.: Gesichtsspalten Gemeinsam mit hand- und Fussspalten, Z. Orthop. 107: 344, 1969.
A c R o B E R M A T I T I S enteropathica is a rare familial condition which begins most commonly at about the fourth month of life. T h e most c o m m o n manifestations are erosions around the mouth, nails, eyelids, anus, genital areas, elbows, knees, and ankles. There is severe paronychia which may lead to loss of nails; alopecia is another feature pointing to the involvement of the ectodermal tissues. Thrush frequently affects the eroded areas as well as the buccal mucosa. Respiratory infections and diarrhea are common and malabsorption may occur. T h e condition has been well reviewed by Heite and Ody. 1-3 Although etiology is still undetermined, successful therapeutic results have been achieved with diiodohydroxyquinoline 4 and an intravenous cotton seed oil emulsion. 5 We report here the beneficial effect of intra-
110
Brie[ clinical and laboratory observations
Fig. 1. Patient before treatment. Note alopecia and presence of some eyebrows and eyelashes. In addition to lesions of face note blepharitis, photophobia, paronychia, and the frown.
v e n o u s casein hydrolysate in t h e t r e a t m e n t of this condition. CASE
REPORT
Patient S. M., a girl, was born on October 10, 1969. The parents were Jewish immigrants from Iraq and were unrelated. The father had recently begun to have asthma. Five other children are alive and well. One sister died of bronchopneumonia at the age of 3 89 months; she had severe erosions of the skin which were diagnosed as varicelliform eczema. Photographic slides of this infant showed lesions strikingly similar to those found in our patient; it seems reasonable to assume that she too had acrodernaatitis enteropathica. Pregnancy and delivery were normal, and birth weight was 3,300 Gin. The infant was completely breast-fed for three months, but the development of bronchopneumonia at this age necessitated admission to hospital. At the age of five months she was readmitted with bronchopneumonia; erosions of the skin were noted for the first time. At the age of 11 months there was severe loss of hair, and the erosions of the skin were typical of acrodermatitis enteropathica. The child also had diarrhea, the severity of which
The Journal o[ Pediatrics January 1973
parallelled the state of her skin. In view of the provisional diagnosis of acrodermatitis enteropathica, it was decided to try treatment with diiodohydroxyquinolinO in a dose of 200 mg. per day; only slight improvement occurred, and after a few weeks this treatment was discontinued. The child's condition deteriorated and she was transferred to the Pediatric Gastroenterology Research Unit of the Shaare Zedek General Hospital. On admission at the age of 14 months, the infant weighed 5.9 Kg. She was irritable, hypotonic, and in a state of malnutrition. She seemed to shun contact with adults and children and preferred to lie facing the wall. She was bald, but the eyelashes and eyebrows were intact. There were severe paronychia, and oozing lesions were spread over the perianaI and perigluteal regions and the knees. Thrush covered the buccal mucosa (Fig. 1). Laboratory values for hemoglobin and total and differential white ceil counts were normal except for some atypical lymphocytes. The sedimentation rate was 65 mm. per hour. The platelet count was normal. Normal values were obtained for blood glucose, urea, electrolytes, calcium, phosphorus, alkaline phosphatase, uric acid, and glutamic p.yruvic transaminase. Serum protein level was 6.2 Gm. per 100 ml. of which 3.4 Gm. was albumin and 2.8 Gm. globulin. Cephalin floceulation was normal and the prothrombin time was 100 per cent. Staphyloccocus was grown from the skin lesions. Hemagglutinating milk antibodies were present in a titer of 1:640, which is high by our standards. Folio acid and vitamin B~2 values were normal. Immunoglobulin G was 2,300 rag. per 100 ml., IgA 210 rag. per 100 ml., and IgM 48 rag. per 100 ml. A 4 day stool collection contained normal amounts of fat. Glucose and sucrose tolerance tests were normal, but the lactose tolerance cm~ce was flat. The fourth part of the duodenum was biopsied for disaccharidase levels and histology. The following disaccharidase levels were found (the normal range of values for our laboratory are in parentheses): lactase 0 (2.4 to 71), sucrase 8.5 (15.8 to 347), and maltase 37.5 (80 to 672). Intestinal biopsy showed some blunting of the villi with inflammatory cell infiltration of the lamina propria. The skin biopsy (performed by Dr. Leah Dollberg) was reported to show marked parakeratosis and some liquefaction degeneration of the basal layer. The upper dermis was edematous and infiltrated b y histiocytes and lymphocytes
Volume 82 Number 1
Brie[ clinical and laboratory observations
with an admixture of a few neutrophilic and eosinophilic leukocytes. The picture was that of subacute dermatitis. The serum levels of essential fatty acids were estimated after deproteinization with dietherethanol (1:3), and the supernate was extracted with petroleum ether. The extract was evaporated, and methyl esterification was carried out. The fluid was assayed in a Packard 7300/ 7400 gas chromatograph. Arachidonic acid, which some authors have found to be low in this condition, 5 constituted 9 and t l per cent, respectively, on two occasions, which is normal; only traces were detected at the third estimation. Urine chromatography for amino acids was normal; no indoles were found in the urine. Blood for this determination was taken in the fasting state at 8 A.M. in order to avoid the effect of diurnal variation. The control subjects were age matched. After deproteinization with sulfosalieylic acid, the supernatant fluid was assayed in a Spinco-Beckman amino acid analyzer. Tyrosine and tryptophane were determined fluorimetrically.~, ; The plasma amino acid values were at the lower range of normal during relapse; some (e.g., serine, proline, and leucine) were below normal. The oral administration of amino acids raised the levels of the plasma amino acids without inducing a remission. CLINICAL
COURSE
I n view of the patient's chronic d i a r r h e a a n d p o o r nutritional state, m a l a b s o r p t i o n was assumed to be present. W e therefore discontinued oral feedings a n d placed her on a regimen of intravenous a l i m e n t a t i o n with 5 p e r cent enzymatic casein hydrolysate (Amigen, T r a v e n o l Labs.) to which we a d d e d dextrose to a final concentration of 10 p e r cent. This solution was a d m i n i s t e r e d at the rate of 150 ml. p e r kilogram of body weight p e r 24 hours. A t the same time the p a t i e n t received ampicillin a n d cloxaeillin, as septicemia was suspected. A m u l t i v i t a m i n p r e p a r a t i o n was given orally. Local treatm e n t was given for Monilia. T w o days after c o m m e n c e m e n t of intravenous a m i n o acid t h e r a p y the skin showed signs of healing. After one week it h a d almost completely healed (Fig. 2). I n addition, the child bec a m e sociable a n d gained 500 Gin. in weight. A f t e r the initial success we r e p e a t e d the
111
Fig. 2. Patient after treatment with intravenous amino acid hydrolysate. Scales and erosions have given place to delicate granulating skin.
administration of intravenous casein hydrolysate on five separate occasions, using either A m i g e n or H y p r o t i g e n ( L a b o r a t o r i don Baxter, S.p.A.), which is also an enzymatic casein hydrolysate. T r e a t m e n t each time was continued for five successive days. Local applications to the skin were omitted, a n d the p a t i e n t received a n o r m a l w a r d diet and no antibiotic therapy. R a p i d and unequivocal healing of the skin was achieved consistently, but each time after a treatment-free interval of 10 days, the skin broke down again. W h e n the same casein hydrolysate was administered at the same rate b u t by intragastric drip, no healing could be observed after seven days of treatment. Thereafter, we administered intravenously single amino acids in a 0.9 p e r cent NaC1 solution at concentrations a n d amounts similar to those present in A m i g e n for that particular amino acid. A t the same time the patient received a n o r m a l w a r d diet. A trial with intravenous t r y p t o p h a n e for five days
112
Brie[ clinical and laboratory observations
was accompanied by a deterioration in the child's condition. T h e use of intravenous lmethionine for five days produced almost complete healing of the skin on one occasion, but three further attempts to bring about healing by an identical regimen were unsuccessful. As Robertson s suggested that tryptophane metabolism in this disease may be disturbed at the level of hydroxylation of kynurenine, it seemed logical to attempt treatment with nicotinamide. We injected 200 mg. daily for seven days without effect. It was felt that the patient may have failed to respond to diiodohydroxyquinoline because the dose previously given was inadequate; we therefore administered the drug orally in a dose of 0.5 Gm. per kilogram per 24 hours. Complete healing of the skin occurred within a week. During the next two months the skin remained in good condition and the patient gained 1.5 Kg. in weight. Although further investigations were indicated in delineating which of the amino acids in the intravenous hydrolysate might have been responsible for bringing about the remission, the dramatic response to diiodohydroxyquinoline in our patient made it unethical to experiment with other intravenous solutions. Robertson s showed that a tryptophane load in patients with acrodermatitis enteropathica results in an accumulation of kynurenine and remarkably low levels of 3-hydroxykynurenine. Decreased activity of kynurenine hydroxylase might explain these findings and might result in nicotinic acid deficiency; however, nicotinamide injections in our patient were without effect. The high level of milk protein antibodies and the absence of duodenal lactase levels we assumed to be secondary to the prolonged diarrhea. After the child's condition had improved, the ingestion of cow's milk produced
The Journal o[ Pediatrics January 1973
no ill effect. There were no clinical signs, therefore, of milk protein or lactose intolerance. Although the mode of action of intravenous casein hydrolysate in acrodermatitis enteropathica remains unknown, there is no doubt that its administration can bring about complete remission and it may prove to be useful in the treatment of patients resistant to other forms of therapy. SUMMARY
A baby with acrodermatitis enteropathica was treated by an intravenous protein hydrolysate. After infusion of this solution for five days, the skin healed completely although temporarily. Oral administration of this hydrotysate was without effect. The possibility of a defect in the absorption of amino acids in this condition was considered, but could not be confirmed by laboratory evidence. REFERENCES
1. HeRe, H. J., and Ody, R.: Die Aerodermatitis Enteropathiea im Lichte der Haufigkeitsanalyse. ][-IV, Dermatol. Hautartzt. 16: 529, 1965. 2. Heite, H. J., and Ody, R.: Die Acrodermatltis Enteropathica im Lichte der Haufigkeitsanalyse. V-IX, Dermatol. Hautartzt. 17: 1, 1966. 3. Heite, H. J., and Ody, R.: Die Acrodermatitis Enteropathiea im Liehte der Haufigkeitsanalyse. X and XI, Dermatol. Hautartzt. 17: 49, 1966. 4. Dillaha, C. J,, Lorincz, A. L., and Aavick, O. R.: Acrodermatitis enteropathica, J. A. M. A. 152: 509, 1953. 5. Cash, R., and Berger, C. K.: Aerodermatitis enteropathica: Defective metabolism of unsaturated fatty acids, J. PEmATR. 74: 717, 1969. 6. Waalkes, T. P., and Udenfriend, S.: A fluorometric method for the estimation of tyrosine in plasma and tissues, J. Lab. Clin. Med. 50: 733, 1957. 7. Denckla, W. D,, and Dewey, H. K.: The determination of tryptophan in plasma liver and urine, J. Lab. Clin. Med. 69: 160, 1967. 8. Robertson, A.: Quoted by Cash, R., 1971. 9. Cash, R,: Proceedings of the Thirteenth International Congress on Pediatrics, Vienna, 1971.
conductive hearing loss. In 1960, tympanotomy on the left revealed absence of the stapes and part of the incus. Subsequently, a Lempert-type fenestration procedure was performed. DISCUSSION The only unequivocal signs of ectodermal dysplasia in the present series are hypodontia and malformed teeth. Anomalies of the hair, skin, and nails were not present. T h e dental signs, in the J. pedigree at least, suggest that they are further examples of the EEC syndrome. T h e bilateral hypodontia and its presence in both maxilla and mandible makes it unlikely to be associated with the unilateral cleft palate anomalies. SUMMARY
The association of conductive hearing loss with the E E C syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip-palate) is decribed in one sporadic case and in a pedigree with four cases in three generations. Hypodontia was demonstrated in two and conductive hearing loss in three of the family members; in one of them there was congenital absence of the stapes and part of the incus.
Treatment of acrodermatitis enteropatbica by intravenous amino acid
bydrolysate S. Freier, M.B.,* J. Faber, M.D., R. Goldstein, Ph.D., and M. Mayer, Ph.D., Jerusalem, Israel From the Pediatric Gastroenterology Research Unit, Shaare Zedek General Hospital, and the Department o[ Clinical Biochemistry, Hebrew University-Hadassah Medical School. ~Reprint address: Pediatric Gastroenterology Research Unit, Shaare Zedek General Hospital, P.O. Box 293, Jerusalem, Israel.
Brie[ clinical and laboratory observations
1 09
The authors would like to thank Dr. B. W. Tanton for his assistance with the preparation of this paper, and the Departments of Pediatrics, Audiology, and Human Genetics of the University of Groningen for perusal of the case history of Case 1. We would also like to thank Dr. David W. Smith for drawing our attention to the recent publications of the EEC syndrome. REFERENCES
1. Coekayne, E. A.: Cleft palate, hare lip, dacryocystitis, and cleft hand and feet, Biometrika 28; 58, 1936. 2. Walker, J. C., and Clodius, L.: The syndromes of cleft lip, cleft palate and lobster-claw deformities of hands and feet, Plast. Reconstr. Surg. 32" 627, 1963. 3. Riidiger, R. A., Haase, W., and Passarge, E.: Association of ectrodactyly, ectodermal dysplasia, and cleft llp-palate: The EEC syndrome, Am. J. Dis. Child. 120: 160, 1970. 4. Bixler, D., Spivack, J., Bennett, J., and Christian, J. C.: The ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome: Report of 2 cases and review of the literature, Clin. Genet. 3: 43, 1971. 5. Wildervanck, L. S.: Perceptive deafness associated with split-hand and foot, a new syndrome? Acta Genet. 13: 161, 1963. 6. Birch-Jensen, A.: Congenital deformities of the upper extremities, Copenhagen, 1949, Ejnar Munksgaards Forlag. 7. Berndorfer, A.: Gesichtsspalten Gemeinsam mit hand- und Fussspalten, Z. Orthop. 107: 344, 1969.
A c R o B E R M A T I T I S enteropathica is a rare familial condition which begins most commonly at about the fourth month of life. T h e most c o m m o n manifestations are erosions around the mouth, nails, eyelids, anus, genital areas, elbows, knees, and ankles. There is severe paronychia which may lead to loss of nails; alopecia is another feature pointing to the involvement of the ectodermal tissues. Thrush frequently affects the eroded areas as well as the buccal mucosa. Respiratory infections and diarrhea are common and malabsorption may occur. T h e condition has been well reviewed by Heite and Ody. 1-3 Although etiology is still undetermined, successful therapeutic results have been achieved with diiodohydroxyquinoline 4 and an intravenous cotton seed oil emulsion. 5 We report here the beneficial effect of intra-
110
Brie[ clinical and laboratory observations
Fig. 1. Patient before treatment. Note alopecia and presence of some eyebrows and eyelashes. In addition to lesions of face note blepharitis, photophobia, paronychia, and the frown.
v e n o u s casein hydrolysate in t h e t r e a t m e n t of this condition. CASE
REPORT
Patient S. M., a girl, was born on October 10, 1969. The parents were Jewish immigrants from Iraq and were unrelated. The father had recently begun to have asthma. Five other children are alive and well. One sister died of bronchopneumonia at the age of 3 89 months; she had severe erosions of the skin which were diagnosed as varicelliform eczema. Photographic slides of this infant showed lesions strikingly similar to those found in our patient; it seems reasonable to assume that she too had acrodernaatitis enteropathica. Pregnancy and delivery were normal, and birth weight was 3,300 Gin. The infant was completely breast-fed for three months, but the development of bronchopneumonia at this age necessitated admission to hospital. At the age of five months she was readmitted with bronchopneumonia; erosions of the skin were noted for the first time. At the age of 11 months there was severe loss of hair, and the erosions of the skin were typical of acrodermatitis enteropathica. The child also had diarrhea, the severity of which
The Journal o[ Pediatrics January 1973
parallelled the state of her skin. In view of the provisional diagnosis of acrodermatitis enteropathica, it was decided to try treatment with diiodohydroxyquinolinO in a dose of 200 mg. per day; only slight improvement occurred, and after a few weeks this treatment was discontinued. The child's condition deteriorated and she was transferred to the Pediatric Gastroenterology Research Unit of the Shaare Zedek General Hospital. On admission at the age of 14 months, the infant weighed 5.9 Kg. She was irritable, hypotonic, and in a state of malnutrition. She seemed to shun contact with adults and children and preferred to lie facing the wall. She was bald, but the eyelashes and eyebrows were intact. There were severe paronychia, and oozing lesions were spread over the perianaI and perigluteal regions and the knees. Thrush covered the buccal mucosa (Fig. 1). Laboratory values for hemoglobin and total and differential white ceil counts were normal except for some atypical lymphocytes. The sedimentation rate was 65 mm. per hour. The platelet count was normal. Normal values were obtained for blood glucose, urea, electrolytes, calcium, phosphorus, alkaline phosphatase, uric acid, and glutamic p.yruvic transaminase. Serum protein level was 6.2 Gm. per 100 ml. of which 3.4 Gm. was albumin and 2.8 Gm. globulin. Cephalin floceulation was normal and the prothrombin time was 100 per cent. Staphyloccocus was grown from the skin lesions. Hemagglutinating milk antibodies were present in a titer of 1:640, which is high by our standards. Folio acid and vitamin B~2 values were normal. Immunoglobulin G was 2,300 rag. per 100 ml., IgA 210 rag. per 100 ml., and IgM 48 rag. per 100 ml. A 4 day stool collection contained normal amounts of fat. Glucose and sucrose tolerance tests were normal, but the lactose tolerance cm~ce was flat. The fourth part of the duodenum was biopsied for disaccharidase levels and histology. The following disaccharidase levels were found (the normal range of values for our laboratory are in parentheses): lactase 0 (2.4 to 71), sucrase 8.5 (15.8 to 347), and maltase 37.5 (80 to 672). Intestinal biopsy showed some blunting of the villi with inflammatory cell infiltration of the lamina propria. The skin biopsy (performed by Dr. Leah Dollberg) was reported to show marked parakeratosis and some liquefaction degeneration of the basal layer. The upper dermis was edematous and infiltrated b y histiocytes and lymphocytes
Volume 82 Number 1
Brie[ clinical and laboratory observations
with an admixture of a few neutrophilic and eosinophilic leukocytes. The picture was that of subacute dermatitis. The serum levels of essential fatty acids were estimated after deproteinization with dietherethanol (1:3), and the supernate was extracted with petroleum ether. The extract was evaporated, and methyl esterification was carried out. The fluid was assayed in a Packard 7300/ 7400 gas chromatograph. Arachidonic acid, which some authors have found to be low in this condition, 5 constituted 9 and t l per cent, respectively, on two occasions, which is normal; only traces were detected at the third estimation. Urine chromatography for amino acids was normal; no indoles were found in the urine. Blood for this determination was taken in the fasting state at 8 A.M. in order to avoid the effect of diurnal variation. The control subjects were age matched. After deproteinization with sulfosalieylic acid, the supernatant fluid was assayed in a Spinco-Beckman amino acid analyzer. Tyrosine and tryptophane were determined fluorimetrically.~, ; The plasma amino acid values were at the lower range of normal during relapse; some (e.g., serine, proline, and leucine) were below normal. The oral administration of amino acids raised the levels of the plasma amino acids without inducing a remission. CLINICAL
COURSE
I n view of the patient's chronic d i a r r h e a a n d p o o r nutritional state, m a l a b s o r p t i o n was assumed to be present. W e therefore discontinued oral feedings a n d placed her on a regimen of intravenous a l i m e n t a t i o n with 5 p e r cent enzymatic casein hydrolysate (Amigen, T r a v e n o l Labs.) to which we a d d e d dextrose to a final concentration of 10 p e r cent. This solution was a d m i n i s t e r e d at the rate of 150 ml. p e r kilogram of body weight p e r 24 hours. A t the same time the p a t i e n t received ampicillin a n d cloxaeillin, as septicemia was suspected. A m u l t i v i t a m i n p r e p a r a t i o n was given orally. Local treatm e n t was given for Monilia. T w o days after c o m m e n c e m e n t of intravenous a m i n o acid t h e r a p y the skin showed signs of healing. After one week it h a d almost completely healed (Fig. 2). I n addition, the child bec a m e sociable a n d gained 500 Gin. in weight. A f t e r the initial success we r e p e a t e d the
111
Fig. 2. Patient after treatment with intravenous amino acid hydrolysate. Scales and erosions have given place to delicate granulating skin.
administration of intravenous casein hydrolysate on five separate occasions, using either A m i g e n or H y p r o t i g e n ( L a b o r a t o r i don Baxter, S.p.A.), which is also an enzymatic casein hydrolysate. T r e a t m e n t each time was continued for five successive days. Local applications to the skin were omitted, a n d the p a t i e n t received a n o r m a l w a r d diet and no antibiotic therapy. R a p i d and unequivocal healing of the skin was achieved consistently, but each time after a treatment-free interval of 10 days, the skin broke down again. W h e n the same casein hydrolysate was administered at the same rate b u t by intragastric drip, no healing could be observed after seven days of treatment. Thereafter, we administered intravenously single amino acids in a 0.9 p e r cent NaC1 solution at concentrations a n d amounts similar to those present in A m i g e n for that particular amino acid. A t the same time the patient received a n o r m a l w a r d diet. A trial with intravenous t r y p t o p h a n e for five days
112
Brie[ clinical and laboratory observations
was accompanied by a deterioration in the child's condition. T h e use of intravenous lmethionine for five days produced almost complete healing of the skin on one occasion, but three further attempts to bring about healing by an identical regimen were unsuccessful. As Robertson s suggested that tryptophane metabolism in this disease may be disturbed at the level of hydroxylation of kynurenine, it seemed logical to attempt treatment with nicotinamide. We injected 200 mg. daily for seven days without effect. It was felt that the patient may have failed to respond to diiodohydroxyquinoline because the dose previously given was inadequate; we therefore administered the drug orally in a dose of 0.5 Gm. per kilogram per 24 hours. Complete healing of the skin occurred within a week. During the next two months the skin remained in good condition and the patient gained 1.5 Kg. in weight. Although further investigations were indicated in delineating which of the amino acids in the intravenous hydrolysate might have been responsible for bringing about the remission, the dramatic response to diiodohydroxyquinoline in our patient made it unethical to experiment with other intravenous solutions. Robertson s showed that a tryptophane load in patients with acrodermatitis enteropathica results in an accumulation of kynurenine and remarkably low levels of 3-hydroxykynurenine. Decreased activity of kynurenine hydroxylase might explain these findings and might result in nicotinic acid deficiency; however, nicotinamide injections in our patient were without effect. The high level of milk protein antibodies and the absence of duodenal lactase levels we assumed to be secondary to the prolonged diarrhea. After the child's condition had improved, the ingestion of cow's milk produced
The Journal o[ Pediatrics January 1973
no ill effect. There were no clinical signs, therefore, of milk protein or lactose intolerance. Although the mode of action of intravenous casein hydrolysate in acrodermatitis enteropathica remains unknown, there is no doubt that its administration can bring about complete remission and it may prove to be useful in the treatment of patients resistant to other forms of therapy. SUMMARY
A baby with acrodermatitis enteropathica was treated by an intravenous protein hydrolysate. After infusion of this solution for five days, the skin healed completely although temporarily. Oral administration of this hydrotysate was without effect. The possibility of a defect in the absorption of amino acids in this condition was considered, but could not be confirmed by laboratory evidence. REFERENCES
1. HeRe, H. J., and Ody, R.: Die Aerodermatitis Enteropathiea im Lichte der Haufigkeitsanalyse. ][-IV, Dermatol. Hautartzt. 16: 529, 1965. 2. Heite, H. J., and Ody, R.: Die Acrodermatltis Enteropathica im Lichte der Haufigkeitsanalyse. V-IX, Dermatol. Hautartzt. 17: 1, 1966. 3. Heite, H. J., and Ody, R.: Die Acrodermatitis Enteropathiea im Liehte der Haufigkeitsanalyse. X and XI, Dermatol. Hautartzt. 17: 49, 1966. 4. Dillaha, C. J,, Lorincz, A. L., and Aavick, O. R.: Acrodermatitis enteropathica, J. A. M. A. 152: 509, 1953. 5. Cash, R., and Berger, C. K.: Aerodermatitis enteropathica: Defective metabolism of unsaturated fatty acids, J. PEmATR. 74: 717, 1969. 6. Waalkes, T. P., and Udenfriend, S.: A fluorometric method for the estimation of tyrosine in plasma and tissues, J. Lab. Clin. Med. 50: 733, 1957. 7. Denckla, W. D,, and Dewey, H. K.: The determination of tryptophan in plasma liver and urine, J. Lab. Clin. Med. 69: 160, 1967. 8. Robertson, A.: Quoted by Cash, R., 1971. 9. Cash, R,: Proceedings of the Thirteenth International Congress on Pediatrics, Vienna, 1971.