Ann Otol RhinollAryngollOl:l992
JUNCTIONAL EPIDERMOLYSIS BULLOSA OF THE LARYNX REPORT OF A CASE AND LITERATURE REVIEW ANDREW N. LIN, MD D. MARTIN CARTER, MD
MD ROBERT F. WARD, MD SHELLEY BERSON,
NEW YORK, NEW YORK
Epidermolysis bullosa (EB) is a group of rare inherited disorders in which minor trauma causes blister formation in the skin and mucosa, including the esophagus. Morbidity varies with the type of disease and ranges from occasional trivial skin blisters to death in infancy. Laryngeal involvement presenting as hoarseness and respiratory distress has been reported in nine patients, five of whom had junctional EB. We present the sixth case of junctional EB with laryngeal involvement, and offer guidelines for otolaryngologists and anesthesiologists caring for these fragile patients. KEY WORDS -
blister, junctional epidermolysis bulIosa, laryngeal stenosis, stridor.
INTRODUCfION
I month of age. By 4 months of age, the child tolerated only small amounts of food by mouth. A decision was then made for gastrostomy placement under local anesthesia. Because ofintermittent upper airway problems during the next few months, he began sleeping with an apnea monitor. According to his mother, he occasionally "turned blue" and coughed out small amounts of blood clots that were thought to be due to oral and esophageal blisters. At 9 months he was evaluated at The Rockefeller University Hospital and entered into the National Epidermolysis Bullosa Registry. An otolaryngology examination showed baseline biphasic stridor and mild retractions. Neck radiographs showed only dilation of the hypopharynx and a small epiglottis.
Epidermolysis bullosa (EB) is a heterogeneous group of rare, heritable disorders characterized by abnormal fragility of the skin. It affects I of every 40,000 live-born infants. 1 Depending on the specific type, morbidity varies from the occasional presence ofskin blisters to widespread cutaneous and mucosal blistering that can result in death in infancy. Laryngeal involvement is a rare but serious complication that has been reported in nine patients. In this report, we present a patient with junctional EB and laryngeal involvement, and discuss management guidelines for the otolaryngologist and anesthesiologist. CASE REPORT
At 10 months the patient underwent direct laryngoscopy in the operating room, after general inhalational anesthesia was induced. A Hopkins laryngoscope was used to reveal a scarred and small epiglottis with some narrowing of the supraglottis, scarred epiglottic folds, and thickened false vocal cords. Touching the mucosal surface ofthe epiglottis caused easy sloughing. Because of the concern that any additional manipulation of the airway would lead to further sloughing and possible scarring, the remainder of the trachea was not examined endoscopically. The patient was continued on close observation and discharged 3 days later after an uneventful postoperative course. He was fed primarily through the gastrostomy, although able to tolerate some oral feedings.
The patient was a 30-month-old boy who was the product ofa normal, full-term pregnancy. Because an older sibling had been stillborn, he was delivered via cesarean section. No cutaneous abnormalities were detected at birth, but his nails were noted to be excessively long. On the third day oflife, blisters had developed under his nails and on his fingers and toes. Electron microscopic examination of a skin biopsy specimen showed blister formation at the level of the lamina lucida - a feature diagnostic of junctional EB. Therapy included use of mupirocin ointment, a topical antibiotic that is especially effective against Staphylococcus aureus. During the first month of life, recurrent oral blisters caused difficulty with feedings. Because of poor weight gain, a nasal jejunostomy tube was placed at
He was well until 29 months of age, when he experienced the sudden onset of coughing and gag-
From the Department of Otolaryngology, The New York Hospital-Cornell Medical Center (Berson, Ward), and the Laboratory for Investigative Dermatology, The Rockefeller University (Lin, Carter), New York, New York. Supported in part by two contracts (AR62269 and AR62270) from the National Institutes of Health for the National Epidermolysis Bullosa Registry, a General Clinical Research Center Grant (MOI-RRooI02) from the National Institutes of Health to the Rockefeller University Hospital, and general support from the Pew Trust, REPRINTS - Robert F. Ward, MD, Dept of Otolaryngology ,Cornell University Medical College, 520 E 70th S1,Starr 541, New York, NY 10021.
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TABLE I. CLASSIFICAnON OF EPIDERMOLYSIS BULLOSA Simplex (epidennolytic) Autosomal dominant Intraepidennal blistering Blistering generally mild Lesions usually heal without scarring unless infected Mucosal involvement usually mild Junctional Autosomal recessive Blistering in lamina lucida Severe blistering in "lethalis" form Dystrophic (dennolytic) Blistering below lamina densa Recessive dystrophic Mittenlike scarring of hands and feet Esophageal involvement Dominant dystrophic Mucosal involvement usually mild
ging while nibbling on food, and turned cyanotic. Within seconds, his father manually dislodged the food from the oropharynx and revived him by performing mouth-to-mouth resuscitation. He was hospitalized with inspiratory and expiratory stridor and suprasternal retractions. He was treated with steroids and placed in a croup tent, and he subsequently improved to his baseline status. He was then transferred to the intensive care unit at New York Hospital-Cornell Medical Center. Four days after the respiratory arrest, direct laryngoscopy showed progression of the scar and stenosis in the supraglottis, epiglottis, and arytenoid area; however, the vocal cords appeared normal. Because of the severity of this respiratory event and progressive decline in his overall respiratory status, the decision was made to perform a tracheotomy. This was an elective, uneventful operation, and a custom tracheotomy tube with a shortened adapter was secured around the neck with a well-padded foam rubber strap. Discharge home was on the seventh postoperative day. Since the tracheotomy, there has been no respiratory distress and no evidence of tracheal blisters or problems from the tracheotomy tube. His voice is good with a speaking valve. COMMENT
Epidermolysis bullosa refers to a group of heterogeneous, heritable disorders in which blister formation occurs at sites of minor trauma. Based on patterns of inheritance and the ultrastructural level of blister formation, three main types are recognized (Table 1). Epidermolysis bullosa simplex is transmitted as an autosomal dominant trait, and blister formation is due to breakdown of the basal cells. The extent of blistering is generally mild, and blisters often heal
without scarring unless they are secondarily infected. Junctional EB is an autosomal recessive disorder characterized by blister formation through the lamina lucida, an electron lucent zone located between the basal cell plasma membrane and the lamina densa. Investigators have noted decreased numbers ofpoorly formed hemidesmosomes at sites of blistering- - a finding that may explain the abnormal cutaneous fragility. In dystrophic EB, separation occurs below the lamina densa, and both recessive and dominant forms exist. In recessive dystrophic EB, abnormal collagenase activity has been implicated in pathogenesis of blister formation.' and patients typically develop mittenlike scarring of the hands and feet. Within each of these major types, subtypes are differentiated on the basis of clinical features such as blister morphology, sites of predilection, type of scarring, and extent of mucosal involvement. Some 16 subtypes are recognized, with the severity ranging from trivial localized blistering to widespread involvement of skin and mucosa, crippling hand deformities, and fatal outcome. There is no cure for any form of EB, but treatment has included the use of topical antibiotic ointments, phenytoin, topical and systemic corticosteroids, and oral vitamin E. Controlling secondary infection, avoiding heat, wearing protective dressings, applying frequent lubrication, and selecting soft foods and nutritional supplements" have been key factors in prolongation of the lives of EB patients. The experimental use ofcultured epidermal autografts derived from suction blisters in clinically uninvolved skin has led to cosmetic and functional improvement in junctional EB. 5 The diagnosis ofjunctional EB in our patient was confirmed by electron microscopic examination of a skin biopsy specimen. Of the five or six types of junctional EB currently recognized, his features are most consistentwith "EB lethalis ofHerlitz-Pearson." These patients are born with extensive blisters in the skin and mouth that often lead to death from overwhelming sepsis within the first few months of life. Perioral crusting is a distinctive feature.s One patient had narrowing of the nares." Mucosal involvement can be extensive, and autopsy examination of one patient showed presence of lesions in the esophagus, stomach, jejunum, ileum, colon, rectum, gallbladder, vagina, urinary bladder, and tracheaf Some patients, however, survive into adulthood''; hence, the term "lethalis" is a misnomer. Because ofextensive blood loss from cutaneous and mucosal erosions, patients may be severely anemic and hypoproteinemic. Growth retardation is common, but intelligence is not adversely affected. We are not aware ofany report oflaryngeal blisters caused by intubation for general anesthesia in pa-
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TABLE 2. LARYNGOTRACHEAL INVOLVEMENT IN 10 PATIENTS WITH EPIDERMOLYSIS BULLOSA
Author Present case
Age at Year Diagnosis Sex Type 29mo M JEB 1992 lethalis
Initial Symptom (Age at Onset)
Laryngoscopy Findings
Radiography Findings
Treatment
Outcome
Stridor and cyanosis, scarred epiglottis, feeding disorder (first month)
Small trachea, sclerotic arytenoids, normal vocal cords
Narrow trachea
Tracheotomy at 3 y
Doing well
Glossop et all'
1984
29mo
M
JEB lethalis
Mild stridor (15 mo)
Narrow supra- Narrow traglottis, cyst chea on aryepiglottic fold, inflammation of mucosa
Dilatation of larynx
Gastrointestinal bleeding, death
Gonzalez and Roth l 6
1989
2mo
M
JEB
Hoarse cry, stridor (29 d)
Bullae on epi- Not reported glottis, glottis, and trachea
Tracheotomy
Death from sepsis
l(enna et al l 7
1986
11 mo
M
Benign JEB
Stridor (at birth)
Narrow subglottic space
Tracheotomy
Decannulation planned at 11/2 y of age
Paller et al l S
1986
14 Y
F
Benign JEB
Hoarseness (infancy)
Ulceration of supraglottis, bulla, postcricoid webbing Thick, scarred vocal cords, tracheal stenosis
Not reported
Vocal cord stripping, tracheotomy at6mo
No evidence of disease at 14y
25y
M
Benign JEB
Hoarseness (childhood)
"Blisters and
Not reported
Voice rest
Resolved in 6mo
Tracheotomy at3 wk
Resolved in 18 d, decannulated
scars"
Thompson et al l 9
1980
3wk
M
Dystrophic
Stridor, retractions (3 wk)
Narrow glottis, interarytenoid and tracheal vesicles
Not reported
Ramadass and
1978
5y
M
Dystrophic
Noisy breathing, hoarseness
Cicatricial stenosis of anterior commissure and between arytenoids
Normal chest None and neek radiographs and barium swallow study findings
Observation
6mo
M
"Prob-
Stridor (4 mo)
Edemaofsupraglottis and subglottis with inflammation
Narrow subglottis
Suction
Death from hemoptysis
"Loss of vocal power" (6 mo)
Subglottic edema, web at cordallevel, posterior scar band
Not reported
Tracheotomy at3 y
Stenotic larynx in spite of web incision and stenting
Thangaveluj"
Shackel-
1982
ford et al21
Cohen et al 22
able dystrophic"
1978
8y
M
Not specified
JED - junctional epidermolysis bullosa.
tients with EB. The anesthesiologist caring for an EB patient does face special challenges. Because the skin is so fragile, any skin sites subject to friction should be properly protected. Adhesives should not be applied directly to the skin. Face masks should be gently applied to the lubricated face in order to avoid blisters on the chin, cheeks, bridge of the nose, and lips. Operations that require anesthesia of short duration should be performed with a soft, air-cushioned face mask. If it is necessary to perform intubation, a small, well-lubricated noncuffed endotracheal tube should be used, and it should be loosely secured to the neck with gauze ribbon rather than tape.l? Microstomia
from tissue contraction of the lips, tongue, palate, uvula, and tonsillar pillars may restrict pharyngeal opening. Teeth are typically dysplastic, so extra protective care must be taken. I I Tracheotomy tubes should be secured to the neck with soft padding. Depolarizing muscle relaxants should be avoided because they may cause muscle twitching. Ketamine dissociative anesthesia can be a useful alternative. Disinfecting solutions should be poured on the skin, not rubbed. 12-14 LARYNGEAL INVOLVEMENT
The literature contains 9 previously reported cases of laryngeal involvement in EB patients (Table
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Berson et al, Junctional Epidermolysis Bullosa
2 1S•22) . We have added a 10th case. Including our present case, 6 of these 10 patients had junctional EB,IS-18 although in I of these cases!" the diagnosis had subsequently been questioned by others. 23 Two had dystrophic EB,19,2O I had "probable dystrophic EB,"21 and the type was not specified in another. 22 We are not aware of detailed descriptions of laryngeal involvement ofEB simplex, but "severe hoarseness" has been noted in patients with the DowlingMeara type ofEB simplex.P' As seen in Table 2, five of the six junctional EB patients were male, 2 months to 25 years of age, with symptoms usually obvious in infancy. The cases represent a spectrum of clinical presentations from hoarseness and stridor to acute respiratory distress from hemoptysis. Accordingly, the larynges were described as having denuded epithelium, edema, ulcerations, cysts, bullae, scars, and webs, often progressing to near-fatal stenoses. Four of six junctional EB patients had a tracheotomy performed l6-18; four patients are reportedly doing well, but two patients died, respectively of gastrointestinal bleeding and hemoptysis complications,lS,16 It appears that the severity of laryngeal involvement is directly related to the age at onset. The patients who develop airway problems in infancy are likely to require airway intervention. CONCLUSION
These cases show that laryngeal involvement is a
rare but serious complication ofEB. Initial symptoms are usually stridor and/or hoarseness, which can occur as early as the neonatal period and should lead to immediate otolaryngologic consultation. This includes careful examination, neck and chest radiography, and probably laryngoscopy. Our patient experienced respiratory arrest at home, and was revived by his father's performing mouth-to-mouth resuscitation. Family members and other individuals caring for these patients should be aware of the serious nature of potential respiratory complications of EB, and should be familiar with cardiopulmonary resuscitation and its appropriate use. Because the number of EB patients with laryngeal involvement reported in the literature is small, it is unclear if prophylactic tracheotomy should be performed in these patients. Although EB primarily affects the skin, it can involve virtually any mucosal surface.l? It is therefore possible that tracheotomy itself may cause sufficient damage to the tracheal mucosa to result in blistering. However, our patient tolerated tracheotomy without incident or subsequent blister development on follow-up examinations, in spite of the obvious friability ofhis laryngeal mucosa; he has benefited, with considerable relief of stridor. Further experience in managing additional patients with laryngeal involvement may be required to better define the role of tracheotomy in these patients.
REFERENCES I. Lin AN, Carter DM. Epidermolysis bullosa: when the skin falls apart. 1 Pediatr 1989;114:249-355. 2. Tidman MI, Eady RAJ. Hemidesmosome heterogeneity in junctional epidermolysis bullosa revealed by morphometric analysis. 1 Invest DermatoI1986;86:51-6. 3. Bauer EA, Tabas M. A perspective on the role of collagenase in recessive dystrophic epidermolysis bullosa. Arch DermatoI1988;124:734-6. 4. Wood C, ed. Round table No.4. Topical mupirocin in epidermolysis bullosa: safety and efficacy of long-term treatment. Proc R Soc Med 1986:12-8. 5. CarterDM,LinAN, VargheseMC,CaldwellD,PrattLA. Eisinger M. Treatment ofjunctional epidermolysis bullosa with epidermal autografts.l Am Acad DermatoI1987;17:246-50. 6. Cross HE. Wells RS, Esterly JR. Inheritance in epidermolysis bullosa lethalis.l Med Genet 1968;5:189-96. 7. Kaluza C, Kennedy Bl, Harman L. Head and neck complications of epidermolysis bullosa. Laryngoscope 1985;95:599-
600. 8. Schachner L, Lazarus OC, Dembitzer H. Epidermolysis bullosa herediteria letha1is: pathology, natural history and therapy. Br 1 DermatoI1977;96:51-8. 9. Pearson RW. Potter E, Strauss F. Epidermolysis bullosa herediteria lethalis. Clinical and histological manifestations and course of disease. Arch DermatoI1974;109:349-55.
10. lames I, Wark H. Airway management during anaesthesia in patients with epidermolysis bullosa dystrophica. Anesthesiology 1982;56:323-6. II. Holbrook KA. Extraneous epithelial involvement in inherited epidermolysis bullosa. Arch DermatoI1988;124:726-31. 12. Nowak AJ. Oropharyngeal lesions and their management in epidermolysis bullosa. Arch DermatoI1988;124:742-5. 13. Hagen R, Langenberg C. Anaesthetic management in patients with epidermolysis bullosa dystrophica. Anaesthesia 1988;43:482-5. 14. Fischer GC, Ray DAA. Airway obstruction in epidermolysis bullosa. Anaesthesia 1989;44:49. 15. GlossopLP,MichaelsL.BaileyCM.Epidermolysisbullosa lethalis in the larynx causing acute respiratory failure: a case presentation and review of the literature. Int 1 Pediatr OtorbinolaryngoI1984;7:281-8. 16. Gonzalez C. Roth R. Laryngotracheal involvement in epidermolysis bullosa. Int 1 Pediatr Otorbinolaryngol 1989; 17:305-11. 17. Kenna MA, Stool SE, Mallory SB. lunctional epidermolysis bullosa of the larynx. Pediatrics 1986;78:172-4. 18. Paller AS, FinelD, Kaplan S, Pearson W. The generalized atrophic benign form ofjunctional epidermolysis bullosa. Arch DermatoI1986;122:704-IO. 19. Thompson lW. Ahmed AR. Dudley lP. Epidermolysis
Downloaded from aor.sagepub.com at CMU Libraries - library.cmich.edu on December 17, 2015
Berson et al, Junctional Epidermolysis Bullosa bullosa dystrophica of the larynx and trachea. Acute airway obstruction. Ann 0101Rhinol LaryngoI1980;89:428-9. 20. Ramadass T. Thangavelu TA. Epidennolysis bullosa and its E.N.T. manifestations. Two case reports. J Laryngol 0101 1978;92:441-6. 21. Shackelford GD, Bauer EA, Graviss ER, McAlister WH. Upper airway and external genital involvement in epidermolysis bullosa dystrophica. Pediatr RadioI1982;143:429-32.
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22. Cohen SR, Landing BH. Isaacs H. Epidermolysis bullosa associated with laryngeal stenosis. Ann 0101 Rhinol Laryngol 1978;87(suppl 52):25-8. 23. Gonzalez A, Schachner L. Miller M. Junctional epidermolysis bullosa of the larynx. Pediatrics 1987;79:1051-2. 24. Buchbinder LH, Lucky AW, Ballard E, et aI. Severe infantile epidermolysis buIlosa simplex, Dowling-Meara type. Arch DennatoI1986;122:190-8.
20TH INTERNATIONAL CONFERENCE ON COCHLEAR IMPLANTS The 20th International Conference on Cochlear Implants will be held June 23-25. 1993. at the Ritz-Carlton Hotel, San Francisco, California. For further information, contact University of California, Extended Programs in Medical Education, Room LS-105, San Francisco, CA 94143-0742; (415) 476-4251.
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JUNCTIONAL EPIDERMOLYSIS BULLOSA OF THE LARYNX REPORT OF A CASE AND LITERATURE REVIEW ANDREW N. LIN, MD D. MARTIN CARTER, MD
MD ROBERT F. WARD, MD SHELLEY BERSON,
NEW YORK, NEW YORK
Epidermolysis bullosa (EB) is a group of rare inherited disorders in which minor trauma causes blister formation in the skin and mucosa, including the esophagus. Morbidity varies with the type of disease and ranges from occasional trivial skin blisters to death in infancy. Laryngeal involvement presenting as hoarseness and respiratory distress has been reported in nine patients, five of whom had junctional EB. We present the sixth case of junctional EB with laryngeal involvement, and offer guidelines for otolaryngologists and anesthesiologists caring for these fragile patients. KEY WORDS -
blister, junctional epidermolysis bulIosa, laryngeal stenosis, stridor.
INTRODUCfION
I month of age. By 4 months of age, the child tolerated only small amounts of food by mouth. A decision was then made for gastrostomy placement under local anesthesia. Because ofintermittent upper airway problems during the next few months, he began sleeping with an apnea monitor. According to his mother, he occasionally "turned blue" and coughed out small amounts of blood clots that were thought to be due to oral and esophageal blisters. At 9 months he was evaluated at The Rockefeller University Hospital and entered into the National Epidermolysis Bullosa Registry. An otolaryngology examination showed baseline biphasic stridor and mild retractions. Neck radiographs showed only dilation of the hypopharynx and a small epiglottis.
Epidermolysis bullosa (EB) is a heterogeneous group of rare, heritable disorders characterized by abnormal fragility of the skin. It affects I of every 40,000 live-born infants. 1 Depending on the specific type, morbidity varies from the occasional presence ofskin blisters to widespread cutaneous and mucosal blistering that can result in death in infancy. Laryngeal involvement is a rare but serious complication that has been reported in nine patients. In this report, we present a patient with junctional EB and laryngeal involvement, and discuss management guidelines for the otolaryngologist and anesthesiologist. CASE REPORT
At 10 months the patient underwent direct laryngoscopy in the operating room, after general inhalational anesthesia was induced. A Hopkins laryngoscope was used to reveal a scarred and small epiglottis with some narrowing of the supraglottis, scarred epiglottic folds, and thickened false vocal cords. Touching the mucosal surface ofthe epiglottis caused easy sloughing. Because of the concern that any additional manipulation of the airway would lead to further sloughing and possible scarring, the remainder of the trachea was not examined endoscopically. The patient was continued on close observation and discharged 3 days later after an uneventful postoperative course. He was fed primarily through the gastrostomy, although able to tolerate some oral feedings.
The patient was a 30-month-old boy who was the product ofa normal, full-term pregnancy. Because an older sibling had been stillborn, he was delivered via cesarean section. No cutaneous abnormalities were detected at birth, but his nails were noted to be excessively long. On the third day oflife, blisters had developed under his nails and on his fingers and toes. Electron microscopic examination of a skin biopsy specimen showed blister formation at the level of the lamina lucida - a feature diagnostic of junctional EB. Therapy included use of mupirocin ointment, a topical antibiotic that is especially effective against Staphylococcus aureus. During the first month of life, recurrent oral blisters caused difficulty with feedings. Because of poor weight gain, a nasal jejunostomy tube was placed at
He was well until 29 months of age, when he experienced the sudden onset of coughing and gag-
From the Department of Otolaryngology, The New York Hospital-Cornell Medical Center (Berson, Ward), and the Laboratory for Investigative Dermatology, The Rockefeller University (Lin, Carter), New York, New York. Supported in part by two contracts (AR62269 and AR62270) from the National Institutes of Health for the National Epidermolysis Bullosa Registry, a General Clinical Research Center Grant (MOI-RRooI02) from the National Institutes of Health to the Rockefeller University Hospital, and general support from the Pew Trust, REPRINTS - Robert F. Ward, MD, Dept of Otolaryngology ,Cornell University Medical College, 520 E 70th S1,Starr 541, New York, NY 10021.
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TABLE I. CLASSIFICAnON OF EPIDERMOLYSIS BULLOSA Simplex (epidennolytic) Autosomal dominant Intraepidennal blistering Blistering generally mild Lesions usually heal without scarring unless infected Mucosal involvement usually mild Junctional Autosomal recessive Blistering in lamina lucida Severe blistering in "lethalis" form Dystrophic (dennolytic) Blistering below lamina densa Recessive dystrophic Mittenlike scarring of hands and feet Esophageal involvement Dominant dystrophic Mucosal involvement usually mild
ging while nibbling on food, and turned cyanotic. Within seconds, his father manually dislodged the food from the oropharynx and revived him by performing mouth-to-mouth resuscitation. He was hospitalized with inspiratory and expiratory stridor and suprasternal retractions. He was treated with steroids and placed in a croup tent, and he subsequently improved to his baseline status. He was then transferred to the intensive care unit at New York Hospital-Cornell Medical Center. Four days after the respiratory arrest, direct laryngoscopy showed progression of the scar and stenosis in the supraglottis, epiglottis, and arytenoid area; however, the vocal cords appeared normal. Because of the severity of this respiratory event and progressive decline in his overall respiratory status, the decision was made to perform a tracheotomy. This was an elective, uneventful operation, and a custom tracheotomy tube with a shortened adapter was secured around the neck with a well-padded foam rubber strap. Discharge home was on the seventh postoperative day. Since the tracheotomy, there has been no respiratory distress and no evidence of tracheal blisters or problems from the tracheotomy tube. His voice is good with a speaking valve. COMMENT
Epidermolysis bullosa refers to a group of heterogeneous, heritable disorders in which blister formation occurs at sites of minor trauma. Based on patterns of inheritance and the ultrastructural level of blister formation, three main types are recognized (Table 1). Epidermolysis bullosa simplex is transmitted as an autosomal dominant trait, and blister formation is due to breakdown of the basal cells. The extent of blistering is generally mild, and blisters often heal
without scarring unless they are secondarily infected. Junctional EB is an autosomal recessive disorder characterized by blister formation through the lamina lucida, an electron lucent zone located between the basal cell plasma membrane and the lamina densa. Investigators have noted decreased numbers ofpoorly formed hemidesmosomes at sites of blistering- - a finding that may explain the abnormal cutaneous fragility. In dystrophic EB, separation occurs below the lamina densa, and both recessive and dominant forms exist. In recessive dystrophic EB, abnormal collagenase activity has been implicated in pathogenesis of blister formation.' and patients typically develop mittenlike scarring of the hands and feet. Within each of these major types, subtypes are differentiated on the basis of clinical features such as blister morphology, sites of predilection, type of scarring, and extent of mucosal involvement. Some 16 subtypes are recognized, with the severity ranging from trivial localized blistering to widespread involvement of skin and mucosa, crippling hand deformities, and fatal outcome. There is no cure for any form of EB, but treatment has included the use of topical antibiotic ointments, phenytoin, topical and systemic corticosteroids, and oral vitamin E. Controlling secondary infection, avoiding heat, wearing protective dressings, applying frequent lubrication, and selecting soft foods and nutritional supplements" have been key factors in prolongation of the lives of EB patients. The experimental use ofcultured epidermal autografts derived from suction blisters in clinically uninvolved skin has led to cosmetic and functional improvement in junctional EB. 5 The diagnosis ofjunctional EB in our patient was confirmed by electron microscopic examination of a skin biopsy specimen. Of the five or six types of junctional EB currently recognized, his features are most consistentwith "EB lethalis ofHerlitz-Pearson." These patients are born with extensive blisters in the skin and mouth that often lead to death from overwhelming sepsis within the first few months of life. Perioral crusting is a distinctive feature.s One patient had narrowing of the nares." Mucosal involvement can be extensive, and autopsy examination of one patient showed presence of lesions in the esophagus, stomach, jejunum, ileum, colon, rectum, gallbladder, vagina, urinary bladder, and tracheaf Some patients, however, survive into adulthood''; hence, the term "lethalis" is a misnomer. Because ofextensive blood loss from cutaneous and mucosal erosions, patients may be severely anemic and hypoproteinemic. Growth retardation is common, but intelligence is not adversely affected. We are not aware ofany report oflaryngeal blisters caused by intubation for general anesthesia in pa-
Downloaded from aor.sagepub.com at CMU Libraries - library.cmich.edu on December 17, 2015
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TABLE 2. LARYNGOTRACHEAL INVOLVEMENT IN 10 PATIENTS WITH EPIDERMOLYSIS BULLOSA
Author Present case
Age at Year Diagnosis Sex Type 29mo M JEB 1992 lethalis
Initial Symptom (Age at Onset)
Laryngoscopy Findings
Radiography Findings
Treatment
Outcome
Stridor and cyanosis, scarred epiglottis, feeding disorder (first month)
Small trachea, sclerotic arytenoids, normal vocal cords
Narrow trachea
Tracheotomy at 3 y
Doing well
Glossop et all'
1984
29mo
M
JEB lethalis
Mild stridor (15 mo)
Narrow supra- Narrow traglottis, cyst chea on aryepiglottic fold, inflammation of mucosa
Dilatation of larynx
Gastrointestinal bleeding, death
Gonzalez and Roth l 6
1989
2mo
M
JEB
Hoarse cry, stridor (29 d)
Bullae on epi- Not reported glottis, glottis, and trachea
Tracheotomy
Death from sepsis
l(enna et al l 7
1986
11 mo
M
Benign JEB
Stridor (at birth)
Narrow subglottic space
Tracheotomy
Decannulation planned at 11/2 y of age
Paller et al l S
1986
14 Y
F
Benign JEB
Hoarseness (infancy)
Ulceration of supraglottis, bulla, postcricoid webbing Thick, scarred vocal cords, tracheal stenosis
Not reported
Vocal cord stripping, tracheotomy at6mo
No evidence of disease at 14y
25y
M
Benign JEB
Hoarseness (childhood)
"Blisters and
Not reported
Voice rest
Resolved in 6mo
Tracheotomy at3 wk
Resolved in 18 d, decannulated
scars"
Thompson et al l 9
1980
3wk
M
Dystrophic
Stridor, retractions (3 wk)
Narrow glottis, interarytenoid and tracheal vesicles
Not reported
Ramadass and
1978
5y
M
Dystrophic
Noisy breathing, hoarseness
Cicatricial stenosis of anterior commissure and between arytenoids
Normal chest None and neek radiographs and barium swallow study findings
Observation
6mo
M
"Prob-
Stridor (4 mo)
Edemaofsupraglottis and subglottis with inflammation
Narrow subglottis
Suction
Death from hemoptysis
"Loss of vocal power" (6 mo)
Subglottic edema, web at cordallevel, posterior scar band
Not reported
Tracheotomy at3 y
Stenotic larynx in spite of web incision and stenting
Thangaveluj"
Shackel-
1982
ford et al21
Cohen et al 22
able dystrophic"
1978
8y
M
Not specified
JED - junctional epidermolysis bullosa.
tients with EB. The anesthesiologist caring for an EB patient does face special challenges. Because the skin is so fragile, any skin sites subject to friction should be properly protected. Adhesives should not be applied directly to the skin. Face masks should be gently applied to the lubricated face in order to avoid blisters on the chin, cheeks, bridge of the nose, and lips. Operations that require anesthesia of short duration should be performed with a soft, air-cushioned face mask. If it is necessary to perform intubation, a small, well-lubricated noncuffed endotracheal tube should be used, and it should be loosely secured to the neck with gauze ribbon rather than tape.l? Microstomia
from tissue contraction of the lips, tongue, palate, uvula, and tonsillar pillars may restrict pharyngeal opening. Teeth are typically dysplastic, so extra protective care must be taken. I I Tracheotomy tubes should be secured to the neck with soft padding. Depolarizing muscle relaxants should be avoided because they may cause muscle twitching. Ketamine dissociative anesthesia can be a useful alternative. Disinfecting solutions should be poured on the skin, not rubbed. 12-14 LARYNGEAL INVOLVEMENT
The literature contains 9 previously reported cases of laryngeal involvement in EB patients (Table
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Berson et al, Junctional Epidermolysis Bullosa
2 1S•22) . We have added a 10th case. Including our present case, 6 of these 10 patients had junctional EB,IS-18 although in I of these cases!" the diagnosis had subsequently been questioned by others. 23 Two had dystrophic EB,19,2O I had "probable dystrophic EB,"21 and the type was not specified in another. 22 We are not aware of detailed descriptions of laryngeal involvement ofEB simplex, but "severe hoarseness" has been noted in patients with the DowlingMeara type ofEB simplex.P' As seen in Table 2, five of the six junctional EB patients were male, 2 months to 25 years of age, with symptoms usually obvious in infancy. The cases represent a spectrum of clinical presentations from hoarseness and stridor to acute respiratory distress from hemoptysis. Accordingly, the larynges were described as having denuded epithelium, edema, ulcerations, cysts, bullae, scars, and webs, often progressing to near-fatal stenoses. Four of six junctional EB patients had a tracheotomy performed l6-18; four patients are reportedly doing well, but two patients died, respectively of gastrointestinal bleeding and hemoptysis complications,lS,16 It appears that the severity of laryngeal involvement is directly related to the age at onset. The patients who develop airway problems in infancy are likely to require airway intervention. CONCLUSION
These cases show that laryngeal involvement is a
rare but serious complication ofEB. Initial symptoms are usually stridor and/or hoarseness, which can occur as early as the neonatal period and should lead to immediate otolaryngologic consultation. This includes careful examination, neck and chest radiography, and probably laryngoscopy. Our patient experienced respiratory arrest at home, and was revived by his father's performing mouth-to-mouth resuscitation. Family members and other individuals caring for these patients should be aware of the serious nature of potential respiratory complications of EB, and should be familiar with cardiopulmonary resuscitation and its appropriate use. Because the number of EB patients with laryngeal involvement reported in the literature is small, it is unclear if prophylactic tracheotomy should be performed in these patients. Although EB primarily affects the skin, it can involve virtually any mucosal surface.l? It is therefore possible that tracheotomy itself may cause sufficient damage to the tracheal mucosa to result in blistering. However, our patient tolerated tracheotomy without incident or subsequent blister development on follow-up examinations, in spite of the obvious friability ofhis laryngeal mucosa; he has benefited, with considerable relief of stridor. Further experience in managing additional patients with laryngeal involvement may be required to better define the role of tracheotomy in these patients.
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20TH INTERNATIONAL CONFERENCE ON COCHLEAR IMPLANTS The 20th International Conference on Cochlear Implants will be held June 23-25. 1993. at the Ritz-Carlton Hotel, San Francisco, California. For further information, contact University of California, Extended Programs in Medical Education, Room LS-105, San Francisco, CA 94143-0742; (415) 476-4251.
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