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Silver nitrate therapy in epidermolysis bullosa hereditaria of the newborn
85 4
Brie[ clinical and laboratory observations
The Journal o[ Pediatrics June 1968
Table I. Arterial thrombosis with and without topical papaverine
Type o[ procedure
Without: July, 1966, to Sept., 1967 Complications Total No. I Per cent
With: March, 1967, to Sept., 1967 Complications Total No. I Per cent
Brachial cutdowns Femoral cutdowns Axillary cutdowns Needle puncture after cutdowns
24 6 5 11
8 2 2 1
33 33 40 9
24 3 1 8
2 1 0 0
8.5 33 0 0
Total
46
13
28
36
3
8
Our initial experience in children with topical 3 per cent papaverine solution suggests it to be a useful adjunct to careful surgical technique and heparinization in preventing thrombosis after arteriotomies. A controlled double-blind study using topical papaverine is planned. SUMMARY Although tissue loss is a rare event following arteriotomy for cardiac catheterization in infants a n d children, the incidence of arterial thrombosis in our series is relatively high. T h e recent use of topical application of 3 per cent papaverine appears to be useful in reducing the incidence of arterial thrombosis in children undergoing cardiac catheterization. REFERENCES
1. Cahill, J. L., Talbert, J. L., Ottesen, O. E., Rowe, R. D. and Haller, J. A.: Arterial complications following cardiac catheterization in infants and children, J. Pediat. Surg. 2: 134, 1967.
Silver nitrate therapy in epi rmolysis bullosa hereditaria of the newborn Louis Keller, M.D. ST, LOUIS, MO.
2. Vlad, P, Hohn, A., and Lambert, E. C.: Retrograde arterial catheterization of left heart: experience with 500 infants and children, Circulation 29: 787, 1964. 3. Mortensen, J. D.: Clinical sequelae from arterial needle puncture, cannulation and incision, Circulation 35: 1118, 1967. 4. Vengsarker, A. S., and Swan, H. J. C.: Arteriotomy for cardiac catheterization and angiocardiography in infants and children, Mayo CIin. Proc. 37: 619, 1962. 5. Voci, G., and Hamer, N. A. J.: Retrograde arterial catheterization of the left ventricle, Am. J. Cardiol. 5: 493, 1960. 6. Aguilar, S., Kaulback, M. G., and Hugenholtz, P. G.: Retrograde arterial catheterization of the left ventricle in 388 patients with special reference to aortic valve disease and coarctation of the aorta, New England J. Med. 274: 312, 1966. 7. Kinmonth, J. B.: The physiology and relief of traumatic arterial spasm, Brit. M. J. 1: 59, 1952. 8. Husson, G. S., and Blackman, M. S.: Arteriotomy for catheterization of the left side o1 the heart in children. New England J. Med. 268: 545, 1963. 9. Schobinger, R. A., and Ruzicka, F, F.: Venipuncture and vascular cutdown, in vascular roentgenology, arteriography, phlebography, lymphography. New York, 1964, the Macmillan Company, p. 27.
EPIDERMOLYSIS BULLOSA HEREDI T A R I A is an uncommon, hereditary disease, the etiology of which is n o t fully u n d e r stood. Severln a n d F a r b e r 1 suggest that the disease m a y be divided into two m a i n categories: (1) the simplex type, which is nondestructive a n d is inherited as a d o m i n a n t
From the Department of Dermatology, St. Louis University School o[ Medicine and the Cardinal Glennon Memorial Hospital for Children, St. Louis, Mo.
Volume 72 Number 6
Brie[ clinical and laboratory observations
855
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Figs. 1-4. Case 1, severe bullous and erosive lesions of body, arms, hands, legs, feet, and buttocks. Photographed 14 hours after delivery. trait, and (2) the dystrophic group, which consists of three types. Type A, the hyperplastic dystrophic type, is transmitted as a dominant character and appears at birth or shortly thereafter. The children usually appear alert and well but develop lesions of the skin, often of the nails and mucous membranes. Healing occurs without scars or may result in thin, atrophic scarring. Improvement results at puberty. Type B, the dystrophic polydysplastic type, is recessive. The lesions occur as in the hyperplastic type, but the children are generally poorly developed, mentally and physically. The mucous mem-
branes of the mouth, eye, respiratory tract, and vagina, as well as the skin and nails, are commonly involved. Congenital defects of the teeth, nails, and hair are frequently observed. Healing results in scar tissue with milia, keloids, pigmentation, and loss of the distal portion of the digits. Many of these children die before reaching maturity. Type C, the letalis or fatal type, was reported by Herlitz 2 to be transmitted on a recessive basis. This type is rare. The infants usually die within weeks or a few months after birth with all the characteristics of the dystrophic polydysplastic type.
856
Brief clinical and laboratory observations
T h e t r e a t m e n t of the dystrophic types, a n d especially of the severe or letalis forms, has not been satisfactory. Various therapeutic measures including cortisone, A C T H , plasma, a n d whole blood transfusions have been used without success. I n November, 1965, an adult patient with epidermolysis bullosa was presented at the G r a n d R o u n d s of the D e p a r t m e n t of Medicine at St. Louis University. Kodachromes of two infants with the letalis type were also shown. D u r i n g the discussion, a house officer remarked on the similarity in appearance of the skin to severe b u r n s and suggested the use of silver n i t r a t e therapy, as for burns. T h e following is a report of the t r e a t m e n t of such a patient. CASE REPORTS
On. Jan. 31, 1966, a premature first-born infant girl, t4 hours after delivery, presented with denuded skin and raw areas on the lower one third of both legs. Erosions were noted on the buttocks, trunk, neck, and upper and lower lips (Figs. 1 to 4). A 0.5 per cent silver nitrate solution, as used for burns, was applied gently with Kling roller gauze of sufficient thickness to reduce pressure and to prevent slippage. During the next two weeks the treatment appeared to be ineffective. New lesions appeared, including sores in the mouth. On Feb. 17, 1966, the infant was transferred to Cardinal Glennon Memorial Hospital where the same regimen was continued with gradual improvement, manifest by healing without scars, and a decrease in new bullae. The infant was hospitalized until June 2, 1966. During this time the silver nitrate therapy, in addition to supportive therapeutic agents such as ACTH and antibiotics, as used previously, were continued. Although many areas healed without scarring, several areas on the knees, elbows, fingers, and toes were scarred severely. The patient was treated to age one year, and is now 24 months of age. There has been a continuous loss of fingernails and toenails; at present, there are no fingernails, and the toenails, except for the fourth one of each foot, are absent. Bullae
The Journal o[ Pediatrics June 1968
appear less frequently, heal without therapy, and she averages about 10 days per month free of blisters. Mouth sores occur occasionally. Crawling causes the knees to blister, and scars form. Standing causes the feet to blister. She stood up at age 10 months but does not stand for an extended time because her feet are painful. She is mentally alert and is thought to be as bright as her cousin of the same age. She has normal facial and scalp hair, sweats normally, and had eight teeth at 20 months of age. At age 20 months she was 27 inches in height and weighed 17 pounds. There is at the present time no clinical evidence of skin staining (argyrosis), or toxic absorption of the 0.5 per cent silver nitrate solution. The electrolyte balance was not disturbed during the course of therapy. Another newborn infant girl entered Cardinal Glennon Hospital Sept. 6, with the same condition, and remained through Oct. 27, 1967. She was treated with silver nitrate compresses as in the case reported with similar results, DISCUSSION It is impossible to draw conclusions reg a r d i n g the efficacy of t r e a t m e n t from the results obtained in one or two patients. Nevertheless, our results with topical silver nitrate application have clearly seemed superior to the t r e a t m e n t used in other cases in which the disease seemed to be of equal severity. I n as rare a condition as epidermolysis bullosa letalis, beneficial results seem worth reporting. Severin and F a r b e r 1 report benefit from the topical use of a highly concentrated corticosteroid preparation, fluocinolone acetonide 0.2 per cent cream, in the dystrophic polydysplastic type. REFERENCES
1. Severin, G. L., and Farber, E. M.: The management of epidermolysis bullosa in children. Effective topical steroid treatment, Arch. Derm. 95: 302, 1967. 2. Herlitz, G.: Kongenitaler, nicht syphilitischer Pemphigus. Eine Ubersicht nebst Beschreibung einer neuen Krankheitsform (Epidermolysis bullosa hereditaria letalis), Acta paediat. 17: 315, 1935.
Brie[ clinical and laboratory observations
The Journal o[ Pediatrics June 1968
Table I. Arterial thrombosis with and without topical papaverine
Type o[ procedure
Without: July, 1966, to Sept., 1967 Complications Total No. I Per cent
With: March, 1967, to Sept., 1967 Complications Total No. I Per cent
Brachial cutdowns Femoral cutdowns Axillary cutdowns Needle puncture after cutdowns
24 6 5 11
8 2 2 1
33 33 40 9
24 3 1 8
2 1 0 0
8.5 33 0 0
Total
46
13
28
36
3
8
Our initial experience in children with topical 3 per cent papaverine solution suggests it to be a useful adjunct to careful surgical technique and heparinization in preventing thrombosis after arteriotomies. A controlled double-blind study using topical papaverine is planned. SUMMARY Although tissue loss is a rare event following arteriotomy for cardiac catheterization in infants a n d children, the incidence of arterial thrombosis in our series is relatively high. T h e recent use of topical application of 3 per cent papaverine appears to be useful in reducing the incidence of arterial thrombosis in children undergoing cardiac catheterization. REFERENCES
1. Cahill, J. L., Talbert, J. L., Ottesen, O. E., Rowe, R. D. and Haller, J. A.: Arterial complications following cardiac catheterization in infants and children, J. Pediat. Surg. 2: 134, 1967.
Silver nitrate therapy in epi rmolysis bullosa hereditaria of the newborn Louis Keller, M.D. ST, LOUIS, MO.
2. Vlad, P, Hohn, A., and Lambert, E. C.: Retrograde arterial catheterization of left heart: experience with 500 infants and children, Circulation 29: 787, 1964. 3. Mortensen, J. D.: Clinical sequelae from arterial needle puncture, cannulation and incision, Circulation 35: 1118, 1967. 4. Vengsarker, A. S., and Swan, H. J. C.: Arteriotomy for cardiac catheterization and angiocardiography in infants and children, Mayo CIin. Proc. 37: 619, 1962. 5. Voci, G., and Hamer, N. A. J.: Retrograde arterial catheterization of the left ventricle, Am. J. Cardiol. 5: 493, 1960. 6. Aguilar, S., Kaulback, M. G., and Hugenholtz, P. G.: Retrograde arterial catheterization of the left ventricle in 388 patients with special reference to aortic valve disease and coarctation of the aorta, New England J. Med. 274: 312, 1966. 7. Kinmonth, J. B.: The physiology and relief of traumatic arterial spasm, Brit. M. J. 1: 59, 1952. 8. Husson, G. S., and Blackman, M. S.: Arteriotomy for catheterization of the left side o1 the heart in children. New England J. Med. 268: 545, 1963. 9. Schobinger, R. A., and Ruzicka, F, F.: Venipuncture and vascular cutdown, in vascular roentgenology, arteriography, phlebography, lymphography. New York, 1964, the Macmillan Company, p. 27.
EPIDERMOLYSIS BULLOSA HEREDI T A R I A is an uncommon, hereditary disease, the etiology of which is n o t fully u n d e r stood. Severln a n d F a r b e r 1 suggest that the disease m a y be divided into two m a i n categories: (1) the simplex type, which is nondestructive a n d is inherited as a d o m i n a n t
From the Department of Dermatology, St. Louis University School o[ Medicine and the Cardinal Glennon Memorial Hospital for Children, St. Louis, Mo.
Volume 72 Number 6
Brie[ clinical and laboratory observations
855
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Figs. 1-4. Case 1, severe bullous and erosive lesions of body, arms, hands, legs, feet, and buttocks. Photographed 14 hours after delivery. trait, and (2) the dystrophic group, which consists of three types. Type A, the hyperplastic dystrophic type, is transmitted as a dominant character and appears at birth or shortly thereafter. The children usually appear alert and well but develop lesions of the skin, often of the nails and mucous membranes. Healing occurs without scars or may result in thin, atrophic scarring. Improvement results at puberty. Type B, the dystrophic polydysplastic type, is recessive. The lesions occur as in the hyperplastic type, but the children are generally poorly developed, mentally and physically. The mucous mem-
branes of the mouth, eye, respiratory tract, and vagina, as well as the skin and nails, are commonly involved. Congenital defects of the teeth, nails, and hair are frequently observed. Healing results in scar tissue with milia, keloids, pigmentation, and loss of the distal portion of the digits. Many of these children die before reaching maturity. Type C, the letalis or fatal type, was reported by Herlitz 2 to be transmitted on a recessive basis. This type is rare. The infants usually die within weeks or a few months after birth with all the characteristics of the dystrophic polydysplastic type.
856
Brief clinical and laboratory observations
T h e t r e a t m e n t of the dystrophic types, a n d especially of the severe or letalis forms, has not been satisfactory. Various therapeutic measures including cortisone, A C T H , plasma, a n d whole blood transfusions have been used without success. I n November, 1965, an adult patient with epidermolysis bullosa was presented at the G r a n d R o u n d s of the D e p a r t m e n t of Medicine at St. Louis University. Kodachromes of two infants with the letalis type were also shown. D u r i n g the discussion, a house officer remarked on the similarity in appearance of the skin to severe b u r n s and suggested the use of silver n i t r a t e therapy, as for burns. T h e following is a report of the t r e a t m e n t of such a patient. CASE REPORTS
On. Jan. 31, 1966, a premature first-born infant girl, t4 hours after delivery, presented with denuded skin and raw areas on the lower one third of both legs. Erosions were noted on the buttocks, trunk, neck, and upper and lower lips (Figs. 1 to 4). A 0.5 per cent silver nitrate solution, as used for burns, was applied gently with Kling roller gauze of sufficient thickness to reduce pressure and to prevent slippage. During the next two weeks the treatment appeared to be ineffective. New lesions appeared, including sores in the mouth. On Feb. 17, 1966, the infant was transferred to Cardinal Glennon Memorial Hospital where the same regimen was continued with gradual improvement, manifest by healing without scars, and a decrease in new bullae. The infant was hospitalized until June 2, 1966. During this time the silver nitrate therapy, in addition to supportive therapeutic agents such as ACTH and antibiotics, as used previously, were continued. Although many areas healed without scarring, several areas on the knees, elbows, fingers, and toes were scarred severely. The patient was treated to age one year, and is now 24 months of age. There has been a continuous loss of fingernails and toenails; at present, there are no fingernails, and the toenails, except for the fourth one of each foot, are absent. Bullae
The Journal o[ Pediatrics June 1968
appear less frequently, heal without therapy, and she averages about 10 days per month free of blisters. Mouth sores occur occasionally. Crawling causes the knees to blister, and scars form. Standing causes the feet to blister. She stood up at age 10 months but does not stand for an extended time because her feet are painful. She is mentally alert and is thought to be as bright as her cousin of the same age. She has normal facial and scalp hair, sweats normally, and had eight teeth at 20 months of age. At age 20 months she was 27 inches in height and weighed 17 pounds. There is at the present time no clinical evidence of skin staining (argyrosis), or toxic absorption of the 0.5 per cent silver nitrate solution. The electrolyte balance was not disturbed during the course of therapy. Another newborn infant girl entered Cardinal Glennon Hospital Sept. 6, with the same condition, and remained through Oct. 27, 1967. She was treated with silver nitrate compresses as in the case reported with similar results, DISCUSSION It is impossible to draw conclusions reg a r d i n g the efficacy of t r e a t m e n t from the results obtained in one or two patients. Nevertheless, our results with topical silver nitrate application have clearly seemed superior to the t r e a t m e n t used in other cases in which the disease seemed to be of equal severity. I n as rare a condition as epidermolysis bullosa letalis, beneficial results seem worth reporting. Severin and F a r b e r 1 report benefit from the topical use of a highly concentrated corticosteroid preparation, fluocinolone acetonide 0.2 per cent cream, in the dystrophic polydysplastic type. REFERENCES
1. Severin, G. L., and Farber, E. M.: The management of epidermolysis bullosa in children. Effective topical steroid treatment, Arch. Derm. 95: 302, 1967. 2. Herlitz, G.: Kongenitaler, nicht syphilitischer Pemphigus. Eine Ubersicht nebst Beschreibung einer neuen Krankheitsform (Epidermolysis bullosa hereditaria letalis), Acta paediat. 17: 315, 1935.