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Epidermolysis bullosa dystrophica with urinary tract involvement
Epidermolysis Bullosa Dystrophica With Urinary Tract Involvement By O. Ekl~f and K. Parkkulainen Stockholm, Sweden 9 A case of epidermolysis bullosa dystrophica (EBD), neonatally corrected atresia of the pylorus and early infantile development of urinary tract manifestations is reported. Owing to misinterpretation of radiologicai findings, instrumental treatment of the urethra was employed. It resulted in complete and permanent obliteration of the lumen. While the skin disorder has remained slight to moderate in severity, recurrent keratitis has resulted in impaired vision. INDEX WORDS: Epidermolysis bullosa dystrophica; pyloric atresia; urethral valves; urethral stricture; conjunctivitis; keratitis.
P I D E R M O L Y S I S bullosa dystrophica (EDB) is a rare hereditary disease characterized by early development of bullae at sites liable to trauma or friction, t 3 In addition mucous membranes lined by stratified squamous or occasionally by columnar epithelium may become involved ~-5 as well as the nails, teeth, and appendicular skeleton. 6'7 The aim of this paper is to report on the second case of urinary tract affliction. The potentially deleterious implications of employed instrumentation are discussed.
E
CASE REPORT Baby UO born on July 6, 1958 was the 1820-g product of an uncomplicated preterm delivery to a 19-year-old mother (father 23 years old), Gravida 1, Para I. At birth polyhydramnios was noticed. On the fourth day of life increasing vomiting and rapid loss of weight induced radiological examination of the stomach, which showed an obstruction of the gastric outlet. At operation a pylorie atresia was found. Following a gastroduodenostomy the boy thrived. A couple of weeks later he developed blisters of the skin and paronychia. Macroscopic hematuria, albuminuria, and urinary infection at 8 weeks of age justified an intravenous urography (IVU). At this examination a slight unilateral dilatation of the upper urinary tract was found. Attempts at micturition cystourethrography (MCU) failed as it proved impossible to pass a catheter into the bladder. Subsequent, recurrent urinary infections have up to the present time been treated with different antibiotics. Another ]VU at 11 months of age demonstrated moderate, bilateral, upper urinary dilatation, reduced bladder capacity with a swollen, irregular mucosa, and a thick bladder wall. This time the MCU succeeded, although the catheterization again proved difficult. The examination revealed a contraction of the bladder neck and slight dilatation of the posterior urethra down to an infracollicular fold interpreted as a valve (Fig. 1). In addition, paraurethral tracts just distal of this structurewere assessed as urethral diverticula. ElectroresecJournal of Pediatric Surgery, Vol. 19, No. 2 (April), 1984
tion of the bladder neck and the anticipated valve failed to relieve the patient's symptoms. In fact, he developed a desquamative balanitis with meatitis and, gradually, a stenosis of the penile and bulbar urethra making micturition painful. Increasing dilatation of the posterior urethra was demonstrated at a repeat MCU (Fig 2). Following a second electroresection and probing of the penile urethra permanent occlusion ensued. Because of a marked, local tendency to scarification attempts at urethral reconstruction failed. A bladder fistula was employed until 1977, when a successful ureterosigmoideostomy was carried out. In 1978 urinary concrements led to a nephrolithotomy. The skin disorder has over the years run a mild to moderately severe course with a slight tendency to local atrophy, hyperkeratosis and tylosis. A certain dystrophy of the nails prevails. There have been virtually no dental problems, nor is there evidence of skeletal changes. During the first year of life several episodes of cyanosis were noticed but no subsequent respiratory problems have evolved. There is no evidence of a heart lesion. The patient is allergic to barbiturates, which has on several occasions complicated employment of general anesthesia. The nostrils have been slightly narrowed due to scarring. In 1964 an anal fistula was treated surgically without residue. Subsequently, episodes of mild proctitis have occasionally caused pain at defecation. Otherwise there have been no gastrointestinal manifestations following the neonatal gastroduodenostomy. Recurrent severe corneal ulcerations, conjunctivitis with symblepharon, and pterygium formation have resulted in impaired vision. DISCUSSION
Our case belong to the group of recessively inherited EBDJ 'z Although no positive information of consanguinity emerges, close familiar relations in previous generations are quite possible. The population of the rural area from which the parents derive is known to be markedly stationary. It has in the past produced other individuals suffering from EBD. The patient's maternal grandfather and an uncle have a proved acute intermittent porfyria. Porfyria has to be considered a differential diagnosis of the patient's skin disorder but remains a From the Department o f Pediatric Radiology and Surgery, Karolinska Hospital, Stockholm, Sweden. Address reprint requests to O. EklOf Department o f Pediatric Radiology, Karolinska Sjukhuset, PO Box 60 500, 104 Ol Stockholm, Sweden. 9 1984 by Grune & Stratton, Inc. 0022-3468/84/1902-0022501.00/0 215
216
Fig. 1. Initial MCU at 11 months of age. Contracted bladder neck. W i d e posterior urethra down to minor anterior fold interpreted as a valve. Distal to this area probably iatrogenic, paraurethral tracts. Distal penile urethra some-
EKL(~F AND PARKKLAINEN
Urinary tract involvement with EBD has been described once before. In 1973 Kretkowski 13 reported on developing dysuria and hydronephrosis in a 3-year-old black boy secondary to stenosis of the urethral meatus. Following a "generous meatotomy" the dysuria disappeared. Postoperative IVPs showed decreasing dilatation of the upper urinary tract. However, an ulceration of the glans penis persisted at the 3-month follow-up and the later course of condition remains obscure. Negative experience with instrumentation with esophageal stenoses 4'7:4 and efforts to avoid regional techniques whenever general anesthesia is needed ~5'16 anticipate the potential hazards associated with similar procedures applied to the urethra. It appears reasonable to surmise that the employed catheterization, electroresection and probing of the urethra, at least accelerated the process of scarification finally resulting in complete and permanent obliteration. Although recently parenteral use of diphenylhydantoin has been reported to have a beneficial effect on skin fragility 17 there is no generally accepted causal treatment of the basic disease.
what narrow.
rather remote possibility as all laboratory tests have been negative in this respect. Concurrence of EBD and pyloric atresia has repeatedly been described. 8-12Including our case, approximately 15% of the patients with this rare gastric anomaly seems to have suffered from the skin disease as well. 11 Both conditions being extremely rare makes a mere coincidence unlikely. It has therefore been suggested that they may be expressions of closely linked genes or even represent the pleiotropic effect of a single one. 10.11 Based on a recent case, Adashi et al ~2expressed the view that the pyloric anomaly, rather than being an independent feature, might be a part of the diffuse dystrophic process. Their case, however, seems to be the only one in support of this theory. Furthermore, in some other cases the obstruction has been purely septal, a finding contradicting suggested evolution. 9:1 But for an anorectal fistula, successfully divided in 1964, and a mild proctitis with brief episodes of painful defecation, no symptoms and signs pertaining to the gastrointestinal tract have been reported in the present case.
Fig. 2. Following electroresection of bladder neck and postulated valve decreasing bladder capacity, wide bladder neck, increasing dilatation of posterior urethra and narrowing of penile and bulbar urethra.
EBD AND URINARY TRACT INVOLVEMENT
217
ADDENDUM
Since submission of the manuscript, the patient was admitted to an outside hospital with pyelonephritis, impaired renal function, and impending uremia. Radiologically established
dilatation of collecting systems and ureters, due to constriction at the ureterosigmoideostomies, called for bilateral nephrostomy. Whether obstruction should be interpreted as caused by inflammation, postoperative fibrosis, or the basic disease (EBD) remains unknown.
REFERENCES
1. Enell H, Hallgren B, Lundkvist H, et al: Epidermolysis bullosa hereditaria dystrophica. II. Family investigation. Acta Derm-Venerol 34:463-473, 1954 2. Gedde-Dahl Jr T: Epidermolysis bullosa. A clinical, genetic and epidermiological study. Universitetsforlaget, Oslo-BergenTroms6, 1970 3. Sehgal VN, Rege VL, Ghosh SK, et al: Dystrophic epidermolysis bullosa. Interesting gastro-intestinal manifestations. Br J Derm 96:389-392, 1977 4. Orlando RC, Bozymski EM, Briggaman RA, et al: Epidermolysis bullosa; Gastrointestinal manifestations. Ann Intern Med 81:203-206, 1974 5. Kabakian HA, Dahmash NS: Pharyngoesophageal manifestations of epidermolysis bullosa. Clin Radiol 29:9194, 1978 6. Alpert M: Roentgen manifestations of epidermolysis bullosa. A JR 78:66-72, 1957 7. Becker MH, Swinyard CA: Epidermolysis bullosa dystrophica in children. Radiology 90:124-128, 1968 8. Korber JS, Glasson M J: Pyloric atresia associated with epidermolysis bullosa. J Pediatr 90:600-601, 1977 9. Pedersen PV: Pyloric atresia and epidermolysis bullosa. J Pediatr 91:852-853, 1977 10. De Groot WG, Postuma R, Hunter AGW: Familial
pyloric atresia associated with epidermolysis bullosa. J Pediatr 92:429-431, 1978 11. E1 Shafie M, Stidham GL, Klippel CH, et al: Pyloric atresia and epidermolysis bullosa letalis: A lethal combination in two premature newborn siblings. J Pediatr Surg 14:446-449, 1979 12. Adashi EY, Louis F J, Vasquez M: An unusual case of epidermolysis bullosa hereditaria letalis with cutaneous scarring and pyloric atresia. J Pediatr 96:443-446, 1980 13. Kretkowski RC: Urinary tract involvement in epidermolysis bullosa. Pediatrics 51:938-941, 1973 14. Fonkalsrud EW, Ament ME: Surgical management of esophageal stricture due to recessive dystrophic epidermolysis bullosa. J Pediatr Surg 12:221-226, 1977 15. Milne B, Rosales JK: Anaesthesia for correction of oesophageal stricture in a patient with recessive epidermolysis bullosa dystrophica: Case report. Canad Anaesth Soc J 27:169-171, 1980 16. von Rauffer L, Landsleitner B, Albers W: Die operativen Behandlungsm6glichkeiten der Epidermolysis bullosa hereditaria. Z Kinderchir 33:175-186, 1981 17. Eisenberg M, Stevens LH, Schofield P J: Epidermolysis bullosa--New therapeutic approaches. Aust J Derm 19:1 8, 1978
P I D E R M O L Y S I S bullosa dystrophica (EDB) is a rare hereditary disease characterized by early development of bullae at sites liable to trauma or friction, t 3 In addition mucous membranes lined by stratified squamous or occasionally by columnar epithelium may become involved ~-5 as well as the nails, teeth, and appendicular skeleton. 6'7 The aim of this paper is to report on the second case of urinary tract affliction. The potentially deleterious implications of employed instrumentation are discussed.
E
CASE REPORT Baby UO born on July 6, 1958 was the 1820-g product of an uncomplicated preterm delivery to a 19-year-old mother (father 23 years old), Gravida 1, Para I. At birth polyhydramnios was noticed. On the fourth day of life increasing vomiting and rapid loss of weight induced radiological examination of the stomach, which showed an obstruction of the gastric outlet. At operation a pylorie atresia was found. Following a gastroduodenostomy the boy thrived. A couple of weeks later he developed blisters of the skin and paronychia. Macroscopic hematuria, albuminuria, and urinary infection at 8 weeks of age justified an intravenous urography (IVU). At this examination a slight unilateral dilatation of the upper urinary tract was found. Attempts at micturition cystourethrography (MCU) failed as it proved impossible to pass a catheter into the bladder. Subsequent, recurrent urinary infections have up to the present time been treated with different antibiotics. Another ]VU at 11 months of age demonstrated moderate, bilateral, upper urinary dilatation, reduced bladder capacity with a swollen, irregular mucosa, and a thick bladder wall. This time the MCU succeeded, although the catheterization again proved difficult. The examination revealed a contraction of the bladder neck and slight dilatation of the posterior urethra down to an infracollicular fold interpreted as a valve (Fig. 1). In addition, paraurethral tracts just distal of this structurewere assessed as urethral diverticula. ElectroresecJournal of Pediatric Surgery, Vol. 19, No. 2 (April), 1984
tion of the bladder neck and the anticipated valve failed to relieve the patient's symptoms. In fact, he developed a desquamative balanitis with meatitis and, gradually, a stenosis of the penile and bulbar urethra making micturition painful. Increasing dilatation of the posterior urethra was demonstrated at a repeat MCU (Fig 2). Following a second electroresection and probing of the penile urethra permanent occlusion ensued. Because of a marked, local tendency to scarification attempts at urethral reconstruction failed. A bladder fistula was employed until 1977, when a successful ureterosigmoideostomy was carried out. In 1978 urinary concrements led to a nephrolithotomy. The skin disorder has over the years run a mild to moderately severe course with a slight tendency to local atrophy, hyperkeratosis and tylosis. A certain dystrophy of the nails prevails. There have been virtually no dental problems, nor is there evidence of skeletal changes. During the first year of life several episodes of cyanosis were noticed but no subsequent respiratory problems have evolved. There is no evidence of a heart lesion. The patient is allergic to barbiturates, which has on several occasions complicated employment of general anesthesia. The nostrils have been slightly narrowed due to scarring. In 1964 an anal fistula was treated surgically without residue. Subsequently, episodes of mild proctitis have occasionally caused pain at defecation. Otherwise there have been no gastrointestinal manifestations following the neonatal gastroduodenostomy. Recurrent severe corneal ulcerations, conjunctivitis with symblepharon, and pterygium formation have resulted in impaired vision. DISCUSSION
Our case belong to the group of recessively inherited EBDJ 'z Although no positive information of consanguinity emerges, close familiar relations in previous generations are quite possible. The population of the rural area from which the parents derive is known to be markedly stationary. It has in the past produced other individuals suffering from EBD. The patient's maternal grandfather and an uncle have a proved acute intermittent porfyria. Porfyria has to be considered a differential diagnosis of the patient's skin disorder but remains a From the Department o f Pediatric Radiology and Surgery, Karolinska Hospital, Stockholm, Sweden. Address reprint requests to O. EklOf Department o f Pediatric Radiology, Karolinska Sjukhuset, PO Box 60 500, 104 Ol Stockholm, Sweden. 9 1984 by Grune & Stratton, Inc. 0022-3468/84/1902-0022501.00/0 215
216
Fig. 1. Initial MCU at 11 months of age. Contracted bladder neck. W i d e posterior urethra down to minor anterior fold interpreted as a valve. Distal to this area probably iatrogenic, paraurethral tracts. Distal penile urethra some-
EKL(~F AND PARKKLAINEN
Urinary tract involvement with EBD has been described once before. In 1973 Kretkowski 13 reported on developing dysuria and hydronephrosis in a 3-year-old black boy secondary to stenosis of the urethral meatus. Following a "generous meatotomy" the dysuria disappeared. Postoperative IVPs showed decreasing dilatation of the upper urinary tract. However, an ulceration of the glans penis persisted at the 3-month follow-up and the later course of condition remains obscure. Negative experience with instrumentation with esophageal stenoses 4'7:4 and efforts to avoid regional techniques whenever general anesthesia is needed ~5'16 anticipate the potential hazards associated with similar procedures applied to the urethra. It appears reasonable to surmise that the employed catheterization, electroresection and probing of the urethra, at least accelerated the process of scarification finally resulting in complete and permanent obliteration. Although recently parenteral use of diphenylhydantoin has been reported to have a beneficial effect on skin fragility 17 there is no generally accepted causal treatment of the basic disease.
what narrow.
rather remote possibility as all laboratory tests have been negative in this respect. Concurrence of EBD and pyloric atresia has repeatedly been described. 8-12Including our case, approximately 15% of the patients with this rare gastric anomaly seems to have suffered from the skin disease as well. 11 Both conditions being extremely rare makes a mere coincidence unlikely. It has therefore been suggested that they may be expressions of closely linked genes or even represent the pleiotropic effect of a single one. 10.11 Based on a recent case, Adashi et al ~2expressed the view that the pyloric anomaly, rather than being an independent feature, might be a part of the diffuse dystrophic process. Their case, however, seems to be the only one in support of this theory. Furthermore, in some other cases the obstruction has been purely septal, a finding contradicting suggested evolution. 9:1 But for an anorectal fistula, successfully divided in 1964, and a mild proctitis with brief episodes of painful defecation, no symptoms and signs pertaining to the gastrointestinal tract have been reported in the present case.
Fig. 2. Following electroresection of bladder neck and postulated valve decreasing bladder capacity, wide bladder neck, increasing dilatation of posterior urethra and narrowing of penile and bulbar urethra.
EBD AND URINARY TRACT INVOLVEMENT
217
ADDENDUM
Since submission of the manuscript, the patient was admitted to an outside hospital with pyelonephritis, impaired renal function, and impending uremia. Radiologically established
dilatation of collecting systems and ureters, due to constriction at the ureterosigmoideostomies, called for bilateral nephrostomy. Whether obstruction should be interpreted as caused by inflammation, postoperative fibrosis, or the basic disease (EBD) remains unknown.
REFERENCES
1. Enell H, Hallgren B, Lundkvist H, et al: Epidermolysis bullosa hereditaria dystrophica. II. Family investigation. Acta Derm-Venerol 34:463-473, 1954 2. Gedde-Dahl Jr T: Epidermolysis bullosa. A clinical, genetic and epidermiological study. Universitetsforlaget, Oslo-BergenTroms6, 1970 3. Sehgal VN, Rege VL, Ghosh SK, et al: Dystrophic epidermolysis bullosa. Interesting gastro-intestinal manifestations. Br J Derm 96:389-392, 1977 4. Orlando RC, Bozymski EM, Briggaman RA, et al: Epidermolysis bullosa; Gastrointestinal manifestations. Ann Intern Med 81:203-206, 1974 5. Kabakian HA, Dahmash NS: Pharyngoesophageal manifestations of epidermolysis bullosa. Clin Radiol 29:9194, 1978 6. Alpert M: Roentgen manifestations of epidermolysis bullosa. A JR 78:66-72, 1957 7. Becker MH, Swinyard CA: Epidermolysis bullosa dystrophica in children. Radiology 90:124-128, 1968 8. Korber JS, Glasson M J: Pyloric atresia associated with epidermolysis bullosa. J Pediatr 90:600-601, 1977 9. Pedersen PV: Pyloric atresia and epidermolysis bullosa. J Pediatr 91:852-853, 1977 10. De Groot WG, Postuma R, Hunter AGW: Familial
pyloric atresia associated with epidermolysis bullosa. J Pediatr 92:429-431, 1978 11. E1 Shafie M, Stidham GL, Klippel CH, et al: Pyloric atresia and epidermolysis bullosa letalis: A lethal combination in two premature newborn siblings. J Pediatr Surg 14:446-449, 1979 12. Adashi EY, Louis F J, Vasquez M: An unusual case of epidermolysis bullosa hereditaria letalis with cutaneous scarring and pyloric atresia. J Pediatr 96:443-446, 1980 13. Kretkowski RC: Urinary tract involvement in epidermolysis bullosa. Pediatrics 51:938-941, 1973 14. Fonkalsrud EW, Ament ME: Surgical management of esophageal stricture due to recessive dystrophic epidermolysis bullosa. J Pediatr Surg 12:221-226, 1977 15. Milne B, Rosales JK: Anaesthesia for correction of oesophageal stricture in a patient with recessive epidermolysis bullosa dystrophica: Case report. Canad Anaesth Soc J 27:169-171, 1980 16. von Rauffer L, Landsleitner B, Albers W: Die operativen Behandlungsm6glichkeiten der Epidermolysis bullosa hereditaria. Z Kinderchir 33:175-186, 1981 17. Eisenberg M, Stevens LH, Schofield P J: Epidermolysis bullosa--New therapeutic approaches. Aust J Derm 19:1 8, 1978