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Hereditary benign intraepithelial dyskeratosis: Report of two cases with prominent oral lesions
634 Brief reports
J AM ACAD DERMATOL OCTOBER 2001
Hereditary benign intraepithelial dyskeratosis: Report of two cases with prominent oral lesions Camille A. Haisley-Royster, MD,a R. Rand Allingham, MD,b Gordon K. Klintworth, MD, PhD,c and Neil S. Prose, MDa Durham, North Carolina Hereditary benign intraepithelial dyskeratosis is a rare autosomal dominant disorder of the oral and ocular mucosa initially described in the Haliwa-Saponi Native American tribe of North Carolina. We describe 2 sisters with the characteristic oral and ocular findings. This entity should be distinguished from several other diseases that cause white lesions in the mouth including white sponge nevus. (J Am Acad Dermatol 2001;45:634-6.)
From the Department of Medicine, Division of Dermatology,a Department of Ophthalmology,b and the Departments of Pathology and Ophthalmology,c Duke University Medical Center. Reprint requests: Neil S. Prose, MD, Department of Medicine, Division of Dermatology, Duke University Medical Center, Box 3252, Durham, NC 27710. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/54/116336 doi:10.1067/mjd.2001.116336
H
ereditary benign intraepithelial dyskeratosis (HBID) is a rare hereditary disorder affecting the oral and ocular mucosa. This condition has been primarily described in the Haliwa-Saponi Native American tribe of North Carolina.1 HBID is characterized by white spongy plaques in the buccal mucosa associated with the typical ocular findings of white conjunctival plaques. The oral lesions of HBID should be considered in
Brief reports 635
J AM ACAD DERMATOL VOLUME 45, NUMBER 4
A
B Fig 1. White spongy plaques on buccal mucosa of older sister (A) and tongue of younger sister (B).
A
B Fig 2. Dilated blood vessels and triangular shaped white plaques on conjunctival mucosa of younger (A) and older (B) sisters.
the differential diagnosis of white lesions in the mouth and must be distinguished from several dermatologic conditions that affect the oral mucosa.
Dilated vessels and white triangular shaped gelatinous plaques were present on the conjunctiva bilaterally (Fig 2). There were no associated cutaneous lesions.
CASE REPORT Two sisters, aged 19 and 16 years, presented with a history of white lesions on the oral mucosa and ocular injection since early childhood. The sisters were members of the Haliwa-Saponi tribe from North Carolina. The oral lesions were asymptomatic, and the ocular lesions were occasionally associated with mild irritation. By report, their father had similar oral and ocular lesions. The affected persons are descendants of the original family with HBID that was documented by Von Sallmann and Paton.1 The older sister had recently given birth to a male infant who was noted to have white patches on the lips within several weeks of delivery. The patients were otherwise healthy. White spongy plaques diffusely covered the buccal mucosa and tongue of both sisters (Fig 1).
DISCUSSION HBID was first described by Von Sallmann and Paton1 in the Haliwa-Saponi Native American tribe in 1960. This group resides predominantly in Halifax and Warren counties in North Carolina. Although the majority of cases have been reported in members of the Haliwa-Saponi tribe living in North Carolina, a few cases have been detected in other states, usually in descendants of North Carolinian ancestors.2,3 HBID has an autosomal dominant mode of inheritance. This entity is characterized by the development of white granular to gelatinous triangular, perilimbal, bulbar conjunctival plaques. The plaques are associated with dilated conjunctival vessels, which are responsible for its most striking feature—“red eyes.” The lesions are typically bilateral and may
636 Brief reports
encircle or extend over the cornea. Onset is usually in early childhood with a persistent waxing and waning course. According to some affected individuals, the severity of the lesions may vary with the seasons; however, this has not been definitively documented. Lesions may be asymptomatic but are frequently associated with ocular irritation, lacrimation, foreign body sensation, or photophobia. Rarely, decreased vision or permanent blindness may occur as a result of corneal involvement. Histopathologic changes of the conjunctival lesions include thickening of the epithelium, vacuolation of the spinous layer, and the presence of multiple dyskeratotic cells. Our patients did not undergo biopsy because of the characteristic clinical findings and an extensive positive family history with numerous histopathologically confirmed cases. The oral lesions were first described in detail in 1960 by Witkop, Graham, and Rucknagel,4 and like those of the bulbar conjunctiva may vary in extent but are usually asymptomatic. Typically, the disorder affects the mucosa of the mouth and lip, ventral surface of the tongue, and floor of the mouth. White, spongy plaques that may vary in thickness form in the mouth and may be thrown into folds. Histopathologic findings in the oral lesions are similar to the ocular findings, with increased epithelial thickness and numerous dyskeratotic cells. Malignant transformation has not been noted in the oral or ocular lesions. The oral findings are very similar in clinical and histopathologic appearance to the white sponge nevus. The white sponge nevus is also inherited in an autosomal dominant pattern and is linked to defects in keratins 4 and 13.5,6 Unlike HBID, white sponge nevus may affect the external genitalia and rectum.7 In addition, the eyes are unaffected in white sponge nevus. Focal epithelial hyperplasia, or Heck disease, is characterized by flesh-colored to white papules primarily located on the mucosa of the mouth and lips.8 This disorder has been reported most frequently in Native Americans and the Eskimos of Greenland. An infection with human papillomavirus types 13 and 32 has been implicated in the causation of this condition. Reported histopathologic findings include
J AM ACAD DERMATOL OCTOBER 2001
acanthosis, occasional koilocytosis, and ballooning degeneration of the keratinocytes. There are no reports of viral studies in HBID. The differential diagnosis of HBID also includes hereditary mucoepithelial dyskeratosis.9,10 This syndrome affects the mucosae, eyes, skin, hair, nails, and lungs and is believed to result from a defect in desmosomes and gap junctions resulting in epithelial dyshesion and dyskeratosis. Characteristic clinical features include nonpainful erythema affecting the conjunctival, oral, nasal, cervical, vaginal, and urethral mucosa. It is also distinguished from HBID by nonscarring alopecia, keratosis pilaris, and an increased susceptibility to infection and fibrocystic lung disease. The genetic cause of HBID has not been elucidated and there is no effective treatment for the oral or ocular lesions. After excision, the abnormal epithelium almost invariably recurs.11 Alleviation of ocular symptoms has been reported with artificial tears. REFERENCES 1. Von Sallmann L, Paton D. Hereditary benign intraepithelial dyskeratosis, I: ocular manifestations. Arch Ophthalmol 1960; 63:421-9. 2. Yanoff M. Hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1968;79:291-3. 3. McLean IW, Riddle PJ, Scruggs JH, Jones DB. Hereditary benign intraepithelial dyskeratosis: a report of two cases from Texas. Ophthalmology 1981;88:164-8. 4. Witkop CJ, Graham JB, Rucknagel DL. Hereditary benign intraepithelial dyskeratosis, II: oral manifestations and hereditary transmission. Arch Pathol 1960;70:696-711. 5. Rugg EL, McLean WHI, Allison WE, Lunny DP, Macleod Felix DH, et al. A mutation in the mucosal keratin K4 is associated with oral white sponge nevus. Nat Genet 1995;11:450-2. 6. Richard G, De Laurenzi V, Didona B, Bale SJ, Compton JG. Keratin 13 mutation underlies the hereditary mucosal epithelial disorder white sponge nevus. Nat Genet 1995;11:453-5. 7. Nichols GE, Cooper PH, Underwood PB Jr, Greer KE. White sponge nevus. Obstet Gynecol 1990;76:545-8. 8. Cohen PR, Hebert AA, Adler-Storthz K. Focal epithelial hyperplasia: Heck disease. Pediatr Dermatol 1993;10:245-51. 9. Scheman AJ, Ray DJ, Witkop CJ, Dahl MV. Hereditary mucoepithelial dysplasia: case report and review of the literature. J Am Acad Dermatol 1989;21:351-7. 10. Rogers M, Kourt G, Cameron A. Hereditary mucoepithelial dysplasia. Pediatr Dermatol 1994;11:133-8. 11. Reed JW, Cashwell F, Klintworth GK. Corneal manifestations of hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1979;97:297-300.
J AM ACAD DERMATOL OCTOBER 2001
Hereditary benign intraepithelial dyskeratosis: Report of two cases with prominent oral lesions Camille A. Haisley-Royster, MD,a R. Rand Allingham, MD,b Gordon K. Klintworth, MD, PhD,c and Neil S. Prose, MDa Durham, North Carolina Hereditary benign intraepithelial dyskeratosis is a rare autosomal dominant disorder of the oral and ocular mucosa initially described in the Haliwa-Saponi Native American tribe of North Carolina. We describe 2 sisters with the characteristic oral and ocular findings. This entity should be distinguished from several other diseases that cause white lesions in the mouth including white sponge nevus. (J Am Acad Dermatol 2001;45:634-6.)
From the Department of Medicine, Division of Dermatology,a Department of Ophthalmology,b and the Departments of Pathology and Ophthalmology,c Duke University Medical Center. Reprint requests: Neil S. Prose, MD, Department of Medicine, Division of Dermatology, Duke University Medical Center, Box 3252, Durham, NC 27710. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/54/116336 doi:10.1067/mjd.2001.116336
H
ereditary benign intraepithelial dyskeratosis (HBID) is a rare hereditary disorder affecting the oral and ocular mucosa. This condition has been primarily described in the Haliwa-Saponi Native American tribe of North Carolina.1 HBID is characterized by white spongy plaques in the buccal mucosa associated with the typical ocular findings of white conjunctival plaques. The oral lesions of HBID should be considered in
Brief reports 635
J AM ACAD DERMATOL VOLUME 45, NUMBER 4
A
B Fig 1. White spongy plaques on buccal mucosa of older sister (A) and tongue of younger sister (B).
A
B Fig 2. Dilated blood vessels and triangular shaped white plaques on conjunctival mucosa of younger (A) and older (B) sisters.
the differential diagnosis of white lesions in the mouth and must be distinguished from several dermatologic conditions that affect the oral mucosa.
Dilated vessels and white triangular shaped gelatinous plaques were present on the conjunctiva bilaterally (Fig 2). There were no associated cutaneous lesions.
CASE REPORT Two sisters, aged 19 and 16 years, presented with a history of white lesions on the oral mucosa and ocular injection since early childhood. The sisters were members of the Haliwa-Saponi tribe from North Carolina. The oral lesions were asymptomatic, and the ocular lesions were occasionally associated with mild irritation. By report, their father had similar oral and ocular lesions. The affected persons are descendants of the original family with HBID that was documented by Von Sallmann and Paton.1 The older sister had recently given birth to a male infant who was noted to have white patches on the lips within several weeks of delivery. The patients were otherwise healthy. White spongy plaques diffusely covered the buccal mucosa and tongue of both sisters (Fig 1).
DISCUSSION HBID was first described by Von Sallmann and Paton1 in the Haliwa-Saponi Native American tribe in 1960. This group resides predominantly in Halifax and Warren counties in North Carolina. Although the majority of cases have been reported in members of the Haliwa-Saponi tribe living in North Carolina, a few cases have been detected in other states, usually in descendants of North Carolinian ancestors.2,3 HBID has an autosomal dominant mode of inheritance. This entity is characterized by the development of white granular to gelatinous triangular, perilimbal, bulbar conjunctival plaques. The plaques are associated with dilated conjunctival vessels, which are responsible for its most striking feature—“red eyes.” The lesions are typically bilateral and may
636 Brief reports
encircle or extend over the cornea. Onset is usually in early childhood with a persistent waxing and waning course. According to some affected individuals, the severity of the lesions may vary with the seasons; however, this has not been definitively documented. Lesions may be asymptomatic but are frequently associated with ocular irritation, lacrimation, foreign body sensation, or photophobia. Rarely, decreased vision or permanent blindness may occur as a result of corneal involvement. Histopathologic changes of the conjunctival lesions include thickening of the epithelium, vacuolation of the spinous layer, and the presence of multiple dyskeratotic cells. Our patients did not undergo biopsy because of the characteristic clinical findings and an extensive positive family history with numerous histopathologically confirmed cases. The oral lesions were first described in detail in 1960 by Witkop, Graham, and Rucknagel,4 and like those of the bulbar conjunctiva may vary in extent but are usually asymptomatic. Typically, the disorder affects the mucosa of the mouth and lip, ventral surface of the tongue, and floor of the mouth. White, spongy plaques that may vary in thickness form in the mouth and may be thrown into folds. Histopathologic findings in the oral lesions are similar to the ocular findings, with increased epithelial thickness and numerous dyskeratotic cells. Malignant transformation has not been noted in the oral or ocular lesions. The oral findings are very similar in clinical and histopathologic appearance to the white sponge nevus. The white sponge nevus is also inherited in an autosomal dominant pattern and is linked to defects in keratins 4 and 13.5,6 Unlike HBID, white sponge nevus may affect the external genitalia and rectum.7 In addition, the eyes are unaffected in white sponge nevus. Focal epithelial hyperplasia, or Heck disease, is characterized by flesh-colored to white papules primarily located on the mucosa of the mouth and lips.8 This disorder has been reported most frequently in Native Americans and the Eskimos of Greenland. An infection with human papillomavirus types 13 and 32 has been implicated in the causation of this condition. Reported histopathologic findings include
J AM ACAD DERMATOL OCTOBER 2001
acanthosis, occasional koilocytosis, and ballooning degeneration of the keratinocytes. There are no reports of viral studies in HBID. The differential diagnosis of HBID also includes hereditary mucoepithelial dyskeratosis.9,10 This syndrome affects the mucosae, eyes, skin, hair, nails, and lungs and is believed to result from a defect in desmosomes and gap junctions resulting in epithelial dyshesion and dyskeratosis. Characteristic clinical features include nonpainful erythema affecting the conjunctival, oral, nasal, cervical, vaginal, and urethral mucosa. It is also distinguished from HBID by nonscarring alopecia, keratosis pilaris, and an increased susceptibility to infection and fibrocystic lung disease. The genetic cause of HBID has not been elucidated and there is no effective treatment for the oral or ocular lesions. After excision, the abnormal epithelium almost invariably recurs.11 Alleviation of ocular symptoms has been reported with artificial tears. REFERENCES 1. Von Sallmann L, Paton D. Hereditary benign intraepithelial dyskeratosis, I: ocular manifestations. Arch Ophthalmol 1960; 63:421-9. 2. Yanoff M. Hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1968;79:291-3. 3. McLean IW, Riddle PJ, Scruggs JH, Jones DB. Hereditary benign intraepithelial dyskeratosis: a report of two cases from Texas. Ophthalmology 1981;88:164-8. 4. Witkop CJ, Graham JB, Rucknagel DL. Hereditary benign intraepithelial dyskeratosis, II: oral manifestations and hereditary transmission. Arch Pathol 1960;70:696-711. 5. Rugg EL, McLean WHI, Allison WE, Lunny DP, Macleod Felix DH, et al. A mutation in the mucosal keratin K4 is associated with oral white sponge nevus. Nat Genet 1995;11:450-2. 6. Richard G, De Laurenzi V, Didona B, Bale SJ, Compton JG. Keratin 13 mutation underlies the hereditary mucosal epithelial disorder white sponge nevus. Nat Genet 1995;11:453-5. 7. Nichols GE, Cooper PH, Underwood PB Jr, Greer KE. White sponge nevus. Obstet Gynecol 1990;76:545-8. 8. Cohen PR, Hebert AA, Adler-Storthz K. Focal epithelial hyperplasia: Heck disease. Pediatr Dermatol 1993;10:245-51. 9. Scheman AJ, Ray DJ, Witkop CJ, Dahl MV. Hereditary mucoepithelial dysplasia: case report and review of the literature. J Am Acad Dermatol 1989;21:351-7. 10. Rogers M, Kourt G, Cameron A. Hereditary mucoepithelial dysplasia. Pediatr Dermatol 1994;11:133-8. 11. Reed JW, Cashwell F, Klintworth GK. Corneal manifestations of hereditary benign intraepithelial dyskeratosis. Arch Ophthalmol 1979;97:297-300.